Ovarian Cancer Survivor Seeks “Compassionate Use” Drug Exemption From BioMarin to Save Her Life

Andrea Sloan, a 7-year survivor of stage 3c ovarian cancer, is seeking a “compassionate use” exemption from pharmaceutical company BioMarin to save her life. Sloan is scheduled to start treatment at the M.D. Anderson Cancer Center on September 5 and would like to obtain access to the “PARP 1/2 inhibitor” drug known as “BMN 673” by that time. A robust grassroots campaign in support of Sloan has emerged on social media and Change.org in an effort to get an affirmative response from BioMarin.

Andrea Sloan, a 7-year, stage 3c survivor of ovarian cancer, is seeking a “compassionate use” investigational cancer drug exemption from pharmaceutical company BioMarin to save her life. Sloan, the executive director of a non-profit that advocates for survivors of domestic violence and abuse, now finds herself forced to publicly advocate for herself in a last chance effort to get the cancer treatment she needs.

Drugs that are being tested but have not yet been approved by the U.S. Food and Drug Administration (FDA) are called “investigational drugs.” These drugs are generally available only to people who are taking part in a clinical trial. The FDA “Expanded Access” protocol — sometimes referred to as a “compassionate use” exemption — involves the use of an investigational drug outside of a clinical trial to treat a patient with a serious or immediately life-threatening disease or condition, who has no comparable or satisfactory alternative treatment options.

FDA regulations allow access to investigational drugs for treatment purposes on a case-by-case basis for an individual patient, or for intermediate-size groups of patients with similar treatment needs who otherwise do not qualify to participate in a clinical trial. Before an investigational drug can qualify for compassionate use, the patient’s physician, the FDA, and the drug manufacturer must approve such use.

Unfortunately, drug manufacturers may not always be willing or able to provide access to a drug outside of their clinical trials. By law, drug companies are not required to make their drug available through the FDA expanded access protocol, or to make more of a drug for that purpose.

Andrea Sloan, a 7-year survivor of stage 3c ovarian cancer, is seeking a compassionate use exemption from pharmaceutical company BioMarin to save her life. Sloan is scheduled to start treatment at the University of Texas M.D. Anderson Cancer Center on September 5, and she would like to obtain access to the “PARP 1/2 inhibitor” drug known as “BMN 673” by that time. A robust grassroots campaign in support of Sloan has emerged on social media and Change.org in an effort to get an affirmative response from BioMarin.

“BioMarin’s BMN 673 offers me the best chance at a long life,” said Sloan. “My doctors and the FDA agree that I am an excellent candidate for this drug and meet the criteria for compassionate use exemption. However, BioMarin’s lack of a policy on compassionate use is preventing me from gaining access to the drug I need to save my life. I respectfully implore them to reconsider and make the ethical decision to help me.” [Emphasis added]

Sloan has endured two full rounds of chemotherapy, five surgeries, and a stem cell transplant. While her cancer remains responsive to treatment, her bone marrow can no longer tolerate traditional therapies. Her world-class oncology team at M.D. Anderson believes that BioMarin’s PARP inhibitor BMN 673, which is currently being tested in a phase I solid tumor clinical trial, is the best option for Sloan’s BRCA-1 gene-mutated form of ovarian cancer.

Unfortunately, Sloan hit a barrier in gaining access to BMN 673. Further enrollment of ovarian cancer patients in the phase I solid tumor trial is now closed, and the publicly announced portion of the trial that will be entering phase III testing is only open to BRCA gene-mutated breast (but not ovarian) cancer patients. Therefore, Sloan is left with the compassionate use exemption as her only option to access the drug she needs to fight her cancer. Based on FDA requirements, Sloan qualifies for the compassionate use exemption. Data emerging from the phase I BMN 673 study suggest that the drug is a safe and effective treatment option for patients with BRCA gene-mutated ovarian cancer.

Moreover, on August 16, 2013, BioMarin announced that its medical study abstract, entitled “PARP inhibition with BMN 673 in ovarian and breast cancer patients with deleterious mutations of BRCA1 and BRCA2,” has been selected as a “late breaking” abstract by the 17th ECCO — 38th ESMO — 32nd ESTRO European Cancer Congress, which will be held from September 27 through October 1, 2013 in Amsterdam, The Netherlands. BioMarin’s oral presentation at the European Cancer Congress (scheduled for September 29, 2013) will include data presented from 28 ovarian cancer patients with deleterious germline (inherited) BRCA gene mutations, including 17 patients from the phase I BMN 673 trial dose escalation cohort (range 100 µg to 1100 µg) and 11 patients from the dose expansion cohort. Presumably, the most recent ovarian cancer patient data to be presented at the European Cancer Congress will expand upon the positive data presented by the company at the 2013 Annual Meeting of the American Society of Clinical Oncology, which indicate that positive RECIST (“Response Evaluation Criteria in Solid Tumors“) and/or CA-125 ovarian cancer patient responses occurred at BMN 673 drug doses ≥ 100 µg/d in 11 out of 17 (64%) BRCA gene-mutated ovarian and peritoneal cancer patients. The positive RECIST medical imaging findings and the CA-125 blood test results highlight the promising effectiveness of BMN 673, albeit among a small group of ovarian cancer patients.

BMN 673 is a targeted therapy designed to disrupt the tumor without traditional chemotherapy drug side effects, thereby making it an optimal treatment for Sloan.

Despite Sloan’s best efforts, she has been unable to convince BioMarin to allow compassionate use of BMN 673. BioMarin, according to Sloan, has not been cooperative, merely citing their lack of a policy on the issue. Sloan, the executive director of a non-profit that advocates for survivors of domestic violence and abuse, now finds herself forced to publicly advocate for herself in a last chance effort to save her life. Sloan is committed to advocating for meaningful reform on this topic and hopes BioMarin will lead by example in starting a national dialogue.

If you would like to help Andrea Sloan obtain compassionate use of BMN 673, please click on this picture and sign her petition at Change.org.

For those interested in supporting Andrea Sloan, please sign her petition on Change.org that urges BioMarin to grant her a compassionate use investigational cancer drug exemption for BMN 673. Also, you can follow Andrea on Twitter at @andi_sloan.

Update:

Yesterday, BioMarin issued a statement to KXAN, an Austin, Texas local affilate of NBC, in response to a in-depth news story that KXAN aired tonight regarding Andrea Sloan’s dire situation. Effectively, BioMarin rejected Andrea Sloan’s request for compassionate use of BMN 673, although its statement was worded as a general drug “expanded access” policy explanation.

BioMarin acknowledged that it allowed preapproved expanded access to one of its investigational drugs which completed phase III clinical testing last year. In terms of general guidelines for its expanded access programs, the company stated:

“We implement these [expanded access] programs when we have sufficient scientific evidence to support both the safety and the efficacy of a product for an indication. Additionally, we implement these programs only when we can ensure that access will be provided equitably, ensuring that the process is appropriately blinded, and when we are confident that the expanded access will not inhibit our clinical trial plans or clinical trials for a disease generally.”

In terms of Andrea Sloan’s specific case, BioMarin stated that it does not comment on the status of individual patients. Apparently in a refusal to grant expanded access to any preapproved patient who requests compassionate use of BMN 673 prior to completion of phase III drug testing, the company stated:

“… However, we note that, although the current data [for BMN 673] that we have looks promising, there is no data at this point to support anything beyond dosing and some preliminary safety. It is too early to know if the experimental therapy is safe or effective, or will even prolong life, until we conduct the appropriate Phase 3 trials. The data that we have is from an ongoing early stage clinical trial, and it is the first trial that we have ever done with this therapy in humans.”

Accordingly, it appears that BioMarin’s current expanded access policy for its investigational drugs, such as BMN 673, will only extend to drugs that have already completed phase III clinical trial testing.

Sources:

• Ovarian Cancer Survivor Andrea Sloan Seeks Compassionate Use Exemption From BioMarin to Save Her Life, Press Release, Digital Journal, August 29, 2013.

• BioMarin Provides BMN 673 Program Update, BioMarin Pharmaceutical Inc, Press Release, July 25, 2013.

• De Bono JS et. al. First-in-human trial of novel oral PARP inhibitor BMN 673 in patients with solid tumors. J Clin Oncol 31, 2013 (suppl; abstr 2580).

• Shen Y. et al.  BMN 673, a novel and highly potent PARP-1/2 inhibitor for the treatment of human cancers with DNA repair deficiency. Clin Cancer Res. 2013 Jul 23. PMID: 23881923 [Epub ahead of print]

• A Phase 1, First in Human, Single-arm, Open-label Study of Once a Day, Orally Administered BMN 673 in Patients With Advanced or Recurrent Solid Tumors. ClinicalTrials.gov Identifier: NCT01286987.

• Advocate for others needs help in a fight for her life, by Shannon Wolfson & Joe Ellis, In-Depth Investigation, KXAN News, August 29, 2013.

• Statement From BioMarin on Expanded Access, August 28, 2013.

• BioMarin Announces Oral Presentation of BMN 673 Most Recent Data on Breast and Ovarian Cancers at the European Cancer Congress 2013, Press Release, August 16, 2013.

FDA Approves Clinical Protocol for Additional Phase 1 Study of TKM-PLK1 in Primary Liver Cancer or Liver Metastases

The U.S. Food and Drug Administration approves the clinical protocol for an additional Phase 1 study of TKM-PLK1 in patients with either primary liver cancer or liver metastases associated with select cancers including ovarian.

RNA Interference

Nucleic acids are molecules that carry genetic information and include DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). Together these molecules form the building blocks of life. DNA contains the genetic code or “blueprint” used in the development and functioning of all living organisms, while one type of RNA (i.e., “messenger RNA” or mRNA) helps to translate that genetic code into proteins by acting as a messenger between the DNA instructions located in the cell nucleus and the protein synthesis which takes place in the cell cytoplasm (i.e., outside the cell nucleus, but inside the outer cell membrane). Accordingly, DNA is first copied or transcribed into mRNA, which, in turn, gets translated or synthesized into protein.

The molecular origin of many diseases results from either the absence or over-production of specific proteins. “RNA interference” (RNAi) is a mechanism through which gene expression is inhibited at the translation stage, thereby disrupting the protein production. RNAi is considered one of the most important discoveries in the field of molecular biology. Andrew Fire, Ph.D., and Craig C. Mello, Ph.D. shared the 2006 Nobel Prize in Physiology or Medicine for work that led to the discovery of the RNAi mechanism.  Because many diseases – cancer, metabolic, infectious and others – are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi offers the potential to revolutionize the way we treat disease and illness by creating a new class of drugs aimed at eliminating specific gene-products or proteins from the cell. RNAi has been convincingly demonstrated in preclinical models of oncology, influenza, hepatitis, high cholesterol, diabetes, macular degeneration, Parkinson’s disease, and Huntington’s disease.

Small Interfering RNA 

While the mechanism itself is termed “RNAi,” the therapeutic agents that exert the effect are known as “small interfering RNAs” or siRNAs. Sequencing of the human genome has provided the information needed to design siRNA therapeutics directed against a wide range of disease-causing proteins. Based on the mRNA sequence for the target protein, a siRNA therapeutic can be designed relatively quickly compared to the time needed to synthesize and screen conventional small molecule drugs. Moreover, siRNA-based therapeutics are able to bind to a target protein mRNA with great specificity. When siRNA are introduced into the cell cytoplasm they are rapidly incorporated into an “RNA-induced silencing complex” (RISC) and guided to the target protein mRNA, which is then cut and destroyed, preventing the subsequent production of the target protein. The RISC can remain stable inside the cell for weeks, destroying many more copies of the target mRNA and maintaining target protein suppression for long periods of time.

To our knowledge, there are no siRNAs approved yet for medical use outside of a clinical trial, however, a number of R&D initiatives and clinical trials are currently underway, with one of the main areas of research focused on delivery. Because siRNAs are large, unstable molecules, they are unable to access target cells. Delivery technology is required to stabilize these drugs in the human blood stream, allow efficient delivery to the target cells, and facilitate uptake and release into the cell cytoplasm. Tekmira Pharmaceuticals Corporation, a leading developer of RNAi therapeutics has focused its research on identifying lipid nanoparticles (LNPs) that can overcome the challenges of delivering siRNAs.

TKM-PLK1 

TKM-PLK1 is being developed as a novel anti-tumor drug in the treatment of cancer. LNPs are particularly well suited for the delivery of siRNA to treat cancer because the lipid nanoparticles preferentially accumulate within tissues and organs having leaky blood vessels, such as cancerous tumors. Once at the target site, LNPs are taken up by tumor cells and the siRNA payload is delivered inside the cell where it reduces expression of the target protein. Through careful selection of the appropriate molecular targets, LNPs are designed to have potent anti-tumor activity yet be well tolerated by healthy tissue adjacent to the tumor.

Tekmira has taken advantage of this passive targeting effect to develop an siRNA directed against PLK1 (polo-like kinase 1), a protein involved in tumor cell proliferation. Inhibition of PLK1 prevents the tumor cell from completing cell division, resulting in cell cycle arrest and cell death.

Because the standard of care for cancer treatment often involves the use of drug combination therapies, Tekmira has selected gene targets for its oncology applications that synergize with conventional drugs that are currently in use. TKM-PLK1 has the potential to provide both direct tumor cell killing and sensitization of tumor cells to the effects of chemotherapy drugs.

Phase 1 Study of TKM-PLK1 in Primary Liver Cancer or Liver Metastases

Tekmira, along with its collaborators at the U.S. National Cancer Institute (NCI), announced that they have received approval from the U.S. Food and Drug Administration (FDA) to proceed with a new Phase 1 clinical trial for Tekmira’s lead oncology product, TKM-PLK1. This trial, run in parallel with the ongoing Phase 1 trial of TKM-PLK1 (for adult patients with solid tumors or lymphomas that are refractory to standard therapy), provides Tekmira with an early opportunity to validate the mechanism of drug action.

“Patients in this new study, who will have either primary liver cancer or liver metastases, will receive TKM-PLK1 delivered directly into the liver via Hepatic Artery Infusion (HAI). The trial design will allow us to measure tumor delivery, polo-like kinase 1 (PLK1) messenger RNA knockdown, and RNA interference (RNAi) activity in tumor biopsies from all of the patients treated,” said Dr. Mark J. Murray, Tekmira’s President and CEO.

“This NCI clinical trial will run in parallel with our multi-center TKM-PLK1 solid tumor Phase 1 trial, currently underway at three centers in the United States. Working together on this clinical trial with our collaborators at the NCI will allow us to develop an even more robust data package to inform subsequent TKM-PLK1 development. We expect to have interim TKM-PLK1 clinical data before the end of 2011,” added Dr. Murray.

The NCI trial is a Phase 1 multiple-dose, dose escalation study testing TKM-PLK1 in patients with unresectable colorectal, pancreatic, gastric, breast, ovarian and esophageal cancers with liver metastases, or primary liver cancers. These patients represent a significant unmet medical need as they are not well served by currently approved treatments.

The primary objectives of the trial include evaluation of the feasibility of administering TKM-PLK1 via HAI, and characterization of the pharmacokinetics and pharmacodynamics of TKM-PLK1. Pharmacodynamic measurements will examine the effect of the drug on the patient’s tumors, specifically aiming to confirm PLK1 knockdown and RNAi activity. Typically reserved for later stage trials, pharmacodynamic measurements are facilitated in this Phase 1 trial in part through the unique capabilities of the NCI Surgery Branch. Secondary objectives of the trial include establishing maximum tolerated dose and to evaluate response rate.

About the National Cancer Institute

The National Cancer Institute (NCI) is one of 27 institutes and centers under the oversight of the U.S. National Institutes of Health (NIH), and is the primary cancer medical research agency in the U.S. The TKM-PLK1 trial will involve investigators at the NCI’s Center for Cancer Research (CCR) on the main NIH campus located in Bethesda, Maryland. The CCR is home to more than 250 scientists and clinicians working in intramural research at the NCI. CCR’s investigators include some of the worlds most experienced basic, clinical, and translational scientists who work together to advance our knowledge of cancer and develop new therapies.

About TKM-PLK1

TKM-PLK1 targets polo-like kinase 1, or PLK1, a cell cycle protein involved in tumor cell proliferation and a validated oncology target. Cancer patients whose tumors express high levels of PLK1 have a relatively poor prognosis. Inhibition of PLK1 prevents tumor cells from completing cell division, resulting in cell cycle arrest and cancer cell death.

About RNAi and Tekmira’s LNP Technology

RNAi therapeutics have the potential to treat a broad number of human diseases by “silencing” disease causing genes. The discoverers of RNAi, a gene silencing mechanism used by all cells, were awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi therapeutics, such as “siRNAs,” require delivery technology to be effective systemically. LNP technology is one of the most widely used siRNA delivery approaches for systemic administration. Tekmira’s LNP technology (formerly referred to as “stable nucleic acid-lipid particles” or SNALP) encapsulates siRNAs with high efficiency in uniform lipid nanoparticles which are effective in delivering RNAi therapeutics to disease sites in numerous preclinical models. Tekmira’s LNP formulations are manufactured by a proprietary method which is robust, scalable and highly reproducible and LNP-based products have been reviewed by multiple FDA divisions for use in clinical trials. LNP formulations comprise several lipid components that can be adjusted to suit the specific application.

About Tekmira Pharmaceuticals Corporation

Tekmira Pharmaceuticals Corporation is a biopharmaceutical company focused on advancing novel RNAi therapeutics and providing its leading lipid nanoparticle delivery technology to pharmaceutical partners. Tekmira has been working in the field of nucleic acid delivery for over a decade and has broad intellectual property covering LNPs. Further information about Tekmira can be found at www.tekmirapharm.com. Tekmira is based in Vancouver, British Columbia, Canada.

Source

• Tekmira Announces Additional Clinical Trial of TKM-PLK1 with the U.S. National Cancer Institute, Press Release, Tekmira Pharmaceuticals Corporation, August 9, 2010.

Clinical Trial Information

• A Phase 1 Dose Escalation Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous TKM-080301 [a/k/a TKM-PLK1 or PLK1 SNALP] in Patients With Advanced Solid Tumors [or Lymphomas], ClinicalTrials.gov Identifier: NCT01262235. [Note: This clinical trial summary relates to the ongoing Phase 1 TKM-PLK1  solid tumor clinical trial. We will post the second Phase 1 TKM-PLK1 clinical trial summary with respect to primary liver cancer and liver metastases once it becomes publicly available]

Additional Information

• RNA Interference: Advancement in Drug Discoveries and Recently Achieved Milestones, Alnylam Pharmaceuticals (www.alnylam.com).

• Wang J, et al. Delivery of siRNA therapeutics: barriers and carriers. AAPS J. 2010 Dec;12(4):492-503. Epub 2010 Jun 11. Review. PubMed PMID: 20544328; PubMed Central PMCID: PMC2977003.

Outside-the-Body Filtration Device May Reduce Ovarian Cancer Cells In Abdominal Fluid

A paper published in the January issue of the journal Nanomedicine could provide the foundation for a new ovarian cancer treatment option — one that would use an outside-the-body filtration device to remove a large portion of the free-floating cancer cells that often create secondary tumors.

Schematic shows how fluids containing ovarian cancer cells could be removed from the body, treated with magnetic nanoparticles to remove the cells, then returned to the body. (Courtesy of Ken Scarberry)

Magnetic nanoparticles suspended in a liquid are attracted to a magnet. The nanoparticles could be attached to cancer cells and then removed from the body with magnetic filtration. (Credit: Gary Meek)

A paper published in the January issue of the journal Nanomedicine could provide the foundation for a new ovarian cancer treatment option — one that would use an outside-the-body filtration device to remove a large portion of the free-floating cancer cells that often create secondary tumors.

Researchers at the Georgia Institute of Technology have formed a startup company and are working with a medical device firm to design a prototype treatment system that would use magnetic nanoparticles engineered to capture cancer cells. Added to fluids removed from a patient’s abdomen, the magnetic nanoparticles would latch onto the free-floating cancer cells, allowing both the nanoparticles and cancer cells to be removed by magnetic filters before the fluids are returned to the patient’s body.

In mice with free-floating ovarian cancer cells, a single treatment with an early prototype of the nanoparticle-magnetic filtration system captured enough of the cancer cells that the treated mice lived nearly a third longer than untreated ones. The researchers expect multiple treatments to extend the longevity benefit, though additional research will be needed to document that — and determine the best treatment options.

“Almost no one dies from primary ovarian cancer,” said Dr. John McDonald, a professor in Georgia Tech’s School of Biology and chief research scientist of Atlanta’s Ovarian Cancer Institute. “You can remove the primary cancer, but the problem is metastasis. A good deal of the metastasis in ovarian cancer comes from cancer cells sloughing off into the abdominal cavity and spreading the disease that way.”

The removal system being developed by McDonald and postdoctoral fellow Ken Scarberry — who is also CEO of startup company Sub-Micro — should slow tumor progression in humans. It may reduce the number of free-floating cancer cells enough that other treatments, and the body’s own immune system, could keep the disease under control.

Professor John McDonald (standing) and postdoctoral fellow Ken Scarberry examine statistical data from their study of a potential new treatment option for ovarian cancer. (Credit: Gary Meek)

“If you can reduce metastasis, you can improve the lifespan of the person with the disease and get a better chance of treating it effectively,” said McDonald. “One goal is to make cancer a chronic disease that can be effectively treated over an extended period of time. If we can’t cure it, perhaps we can help people to live with it.”

Earlier in vitro studies published by the authors of the Nanomedicine paper showed that the magnetic nanoparticles could selectively remove human ovarian cancer cells from ascites fluid, which builds up in the peritoneal cavities of ovarian cancer patients. The nanoparticles are engineered with ligands that allow them to selectively attach to cancer cells.

The researchers believe that treating fluid removed from the body avoids potential toxicity problems that could result from introducing the nanoparticles into the body, though further studies are needed to confirm that the treatment would have no adverse effects.

The recently reported study in Nanomedicine used three sets of female mice to study the benefit of the nanoparticle-magnetic filtration system. Each mouse was injected with approximately 500,000 murine ovarian cancer cells, which multiply rapidly — each cell doubling within approximately 15 hours.

In the experimental group, the researchers — who included research scientist Roman Mezencev — removed fluid from the abdomens of the mice immediately after injection of the cancer cells. They then added the magnetic nanoparticles to the fluid, allowed them to mix, then magnetically removed the nanoparticles along with the attached cancer cells before returning the fluid. The steps were repeated six times for each mouse.

One control group received no treatment at all, while a second control group underwent the same treatment as the experimental group — but without the magnetic nanoparticles. Mice in the two control groups survived a median of 37 days, while the treated mice lived 12 days longer — a 32 percent increase in longevity.

Though much more research must be done before the technique can be tested in humans, McDonald and Scarberry envision a system very similar to what kidney dialysis patients now use, but with a buffer solution circulated through the peritoneal cavity to pick up the cancer cells.

“What we are developing is akin to hemofiltration or peritoneal dialysis in which the patient could come into a clinic and be hooked up to the device a couple of times a week,” said Scarberry. “The treatment is not heavily invasive, so it could be repeated often.”

The new treatment could be used in conjunction with existing chemotherapy and radiation. Reducing the number of free-floating cancer cells could allow a reduction in chemotherapy, which often has debilitating side effects, Scarberry said. The new treatment system could be used to capture spilled cancer cells immediately after surgery on a primary tumor.

The researchers hope to have a prototype circulation and filtration device ready for testing within three years. After that will come studies into the best treatment regimen, examining such issues as the number of magnetic nanoparticles to use, the number of treatments and treatment spacing. If those are successful, the company will work with the FDA to design human clinical trials.

The researchers also studying how their magnetic nanoparticles could be engineered to capture ovarian cancer stem cells, which are not affected by existing chemotherapy. Removing those cells could help eliminate a potent source of new cancer cells.

The research has been supported by the Georgia Research Alliance (GRA), the Ovarian Cancer Institute, the Robinson Family Foundation and the Deborah Nash Harris Endowment. A member of Georgia Tech’s Advanced Technology Development Center (ATDC) startup accelerator program and a GRA VentureLab company, Sub-Micro has also raised private funding to support its prototype development.

Challenges ahead include ensuring that nanoparticles cannot bypass the filtration system to enter the body, and controlling the risk of infection caused by opening the peritoneal cavity.

Beyond cancer, the researchers believe their approach could be useful for treating other diseases in which a reduction in circulating cancer cells or virus particles could be useful. Using magnetic nanoparticles engineered to capture HIV could help reduce viral content in the bloodstream, for instance.

“A technology like this has many different possibilities,” said Scarberry. “We are currently developing the technology to control the metastatic spread of ovarian cancer, but once we have a device that can efficiently and effectively isolate cancer cells from circulating fluids, including blood, we would have other opportunities.”

Sources:

• Study Suggests New Treatment Option For Ovarian Cancer, Press Release, Georgia Institute of Technology, January 26, 2011.

• Scarberry KE, Mezencev R, McDonald JF.  Targeted removal of migratory tumor cells by functionalized magnetic nanoparticles impedes metastasis and tumor progression.  Nanomedicine (Lond). 2011 Jan;6(1):69-78.

Additional Information:

• Removal of Ovarian Cancer Cells From Human Ascites Fluid Using Magnetic Nanoparticles, by Paul Cacciatore, Libby’s H*O*P*E*™, February 1, 2010.

Genentech Announces Positive Results of Avastin Phase III Study in Women with Advanced Ovarian Cancer

Genentech announces positive results of Avastin Phase III study (GOG 218) in women with advanced ovarian cancer. The study showed that women who continued maintenance use of Avastin alone, after receiving Avastin in combination with chemotherapy, lived longer without the disease worsening compared to those who received chemotherapy alone. This is the first Phase III study of an anti-angiogenic therapy in advanced ovarian cancer to meet its primary endpoint.

Tumor angiogenesis is the proliferation of a network of blood vessels that penetrates into cancerous growths, supplying nutrients and oxygen and removing waste products. Tumor angiogenesis actually starts with cancerous tumor cells releasing molecules that send signals to surrounding normal host tissue. This signaling activates certain genes in the host tissue that, in turn, make proteins to encourage growth of new blood vessels. Photo credit: NCI

Genentech, Inc., a wholly owned member of the Roche Group , today announced that a Phase III study showed the combination of Avastin® (bevacizumab) and chemotherapy followed by maintenance use of Avastin alone increased the time women with previously untreated advanced ovarian cancer lived without the disease worsening (progression-free survival or PFS), compared to chemotherapy alone. A preliminary assessment of safety noted adverse events previously observed in pivotal trials of Avastin. Data from the study will be submitted for presentation at the American Society of Clinical Oncology (ASCO) annual meeting, June 4 – 8, 2010.

In the three-arm study, known as Gynecologic Oncology Group (GOG) 0218, women with newly diagnosed advanced ovarian cancer who already had surgery to remove as much of the tumor as possible were randomized to receive one of the following:

• Arm 1: Placebo in combination with carboplatin and paclitaxel chemotherapy followed by placebo alone, for a total of up to 15 months of therapy

• Arm 2: Avastin in combination with carboplatin and paclitaxel chemotherapy followed by placebo alone, for a total of up to 15 months of therapy

• Arm 3: Avastin in combination with carboplatin and paclitaxel chemotherapy followed by the maintenance use of Avastin alone, for a total of up to 15 months of therapy.

The study showed that women who continued maintenance use of Avastin alone, after receiving Avastin in combination with chemotherapy (Arm 3), lived longer without the disease worsening compared to those who received chemotherapy alone. Women who received Avastin in combination with chemotherapy, but did not continue maintenance use of Avastin alone (Arm 2), did not live longer without the disease worsening compared to chemotherapy alone.

“Additional medicines are urgently needed for women with newly diagnosed advanced ovarian cancer, as most women’s cancer will worsen after their initial treatment,” said Hal Barron, M.D., F.A.C.C., Executive Vice President, Global Development and Chief Medical Officer. “We are encouraged by the positive findings of this study, which highlight the importance of continuing maintenance Avastin after combining Avastin with chemotherapy in this setting. We will discuss these results with the U.S. Food and Drug Administration.”

Robert Allen Burger, MD, FACOG, FACS, Fox Chase Cancer Center, Philadelphia, Pennsylvania

“This is good news for women with ovarian, primary peritoneal or fallopian tube cancers,” said GOG 0218 study chair Robert Burger, M.D., Fox-Chase Cancer Center in Philadelphia. “This study showed that after initial surgery, the combination of Avastin and chemotherapy followed by extended treatment with Avastin improves progression-free survival in women with newly diagnosed advanced tumors.”

The trial is sponsored by the National Cancer Institute (NCI) under a Cooperative Research and Development Agreement between the NCI and Genentech, and is being conducted by a network of researchers led by the GOG.

Avastin is being studied worldwide in more than 450 clinical trials for multiple types of cancer, including approximately 25 ongoing clinical trials in the United States for women with various stages of ovarian cancer.

About Ovarian Cancer

According to the American Cancer Society, ovarian cancer is the fifth leading cause of cancer death among American women. In 2009 an estimated 21,500 women were diagnosed with ovarian cancer and approximately 14,500 died from the disease in the U.S. The disease causes more deaths than any other gynecologic cancer, and the American Cancer Society estimates that nearly 70 percent of women with advanced disease will die from it within five years.

Ovarian cancer is associated with high levels of vascular endothelial growth factor (VEGF), a protein associated with tumor growth and spread. Studies have shown a correlation between a high level of VEGF and a poorer prognosis in women with ovarian cancer. Currently, treatment options for women with this disease are limited to surgery and chemotherapy.

About the GOG 0218 Study

GOG 0218 is an international, multicenter, randomized, double-blind, placebo-controlled Phase III study in 1,873 women with previously untreated advanced epithelial ovarian, primary peritoneal or fallopian tube carcinoma. The study evaluates Avastin (5 cycles) in combination with carboplatin and paclitaxel chemotherapy (6 cycles) compared to carboplatin and paclitaxel chemotherapy alone (6 cycles). The trial is also designed to assess the maintenance use of Avastin alone following the initial combined regimen of Avastin and chemotherapy (for a total of up to 15 months of therapy), compared to carboplatin and paclitaxel chemotherapy alone (6 cycles).

The primary endpoint of the study is PFS as assessed by trial investigators. Secondary and exploratory endpoints of the study include overall survival, PFS by independent review, objective response rate, safety, quality of life measures and analysis of patient tumor and blood samples.

Detailed safety assessments are ongoing. A preliminary assessment of safety performed by the GOG identified Avastin-related serious adverse events noted in previous pivotal studies, including fatal neutropenic infection and gastrointestinal perforation. The full study results, including safety information, will be presented at a future medical meeting.

About Avastin

Avastin is a solution for intravenous infusion and is a biologic antibody designed to specifically bind to a protein called VEGF. VEGF plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels, a process known as angiogenesis. Avastin interferes with the tumor blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. Avastin does not bind to receptors on normal or cancer cells. The tumor blood supply is thought to be critical to a tumor’s ability to grow and spread in the body (metastasize). For more information about angiogenesis, visit http://www.gene.com.

Boxed WARNINGS and Additional Important Safety Information

People treated with Avastin may experience side effects. In clinical trials, some people treated with Avastin experienced serious and sometimes fatal side effects, including:

Gastrointestinal (GI) perforation: Treatment with Avastin can result in the development of a potentially serious side effect called GI perforation, which is the development of a hole in the stomach, small intestine or large intestine. In clinical trials, this side effect occurred in more people who received Avastin than in the comparison group (0.3 percent to 2.4 percent). In some cases, GI perforation resulted in fatality.

Surgery and wound healing problems: Treatment with Avastin can lead to slow or incomplete wound healing (for example, when a surgical incision has trouble healing or staying closed). In some cases, this event resulted in fatality. Surgery and wound healing problems occurred more often in people who received Avastin than in the comparison group. Avastin therapy should not be started for at least 28 days after surgery and until the surgical wound is fully healed. The length of time between stopping Avastin and having voluntary surgery without the risk of having surgery and wound healing problems following surgery has not been determined.

Severe bleeding: Treatment with Avastin can result in serious bleeding, including coughing up blood, bleeding in the stomach, vomiting of blood, bleeding in the brain, nosebleeds and vaginal bleeding. These events occurred up to five times more often in people who received Avastin. Across cancer types, 1.2 percent to 4.6 percent of people who received Avastin experienced severe to fatal bleeding. People who have recently coughed up blood (greater than or equal to a half teaspoon of red blood) or have serious bleeding should not receive Avastin.

In clinical trials for different cancer types, there were additional serious and sometimes fatal side effects that occurred in more people who received Avastin than in those in the comparison group. The formation of an abnormal passage from parts of the body to another part (non-GI fistula formation) was seen in 0.3 percent or less of people. Severe to life-threatening stroke or heart problems were seen in 2.4 percent of people. Too much protein in the urine, which led to kidney problems, was seen in less than 1 percent of people. Additional serious side effects that occurred in more people who received Avastin than those in the comparison group included severe to life-threatening high blood pressure, which was seen in 5 percent to 18 percent of people, and nervous system and vision disturbances (reversible posterior leukoencephalopathy syndrome), which was seen in less than 0.1 percent of people. Infusion reactions with the first dose of Avastin were uncommon and occurred in less than 3 percent of people and severe reactions occurred in 0.2 percent of people.

Common side effects that occurred in more than 10 percent of people who received Avastin for different cancer types, and at least twice the rate of the comparison group, were nosebleeds, headache, high blood pressure, inflammation of the nose, too much protein in the urine, taste change, dry skin, rectal bleeding, tear production disorder, back pain and inflammation of the skin (exfoliative dermatitis). Across all trials, treatment with Avastin was permanently stopped in 8.4 percent to 21 percent of people because of side effects.

Avastin may impair fertility. Patients who are pregnant or thinking of becoming pregnant should talk with their doctor about the potential risk of loss of the pregnancy or the potential risk of Avastin to the fetus during and following Avastin therapy, and the need to continue an effective birth control method for at least six months following the last dose of Avastin.

For full Prescribing Information and Boxed WARNINGS on Avastin please visit http://www.avastin.com.

About Genentech

Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a wholly owned member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

About The Gynecologic Oncology Group (GOG)

The Gynecologic Oncology Group is a non-profit organization of more than 300 member institutions with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of Gynecologic malignancies. The Group is committed to maintaining the highest standards in the clinical trial development, execution, analysis and distribution of results. Continuous evaluation of our processes is utilized in order to constantly improve the quality of patient care.

GOG receives support from the National Cancer Institute (NCI) of the National Institutes for Health (NIH).

Sources:

• Genentech Announces Positive Results of Avastin Phase III Study in Women with Advanced Ovarian Cancer, Press Release, Genentech, Inc., February 24, 2010.

• A Phase III Trial of Carboplatin and Paclitaxel Plus Placebo Versus Carboplatin and Paclitaxel Plus Concurrent Bevacizumab (NSC # 704865, IND #7921) Followed By Placebo, Versus Carboplatin and Paclitaxel Plus Concurrent and Extended Bevacizumab, in Women With Newly Diagnosed, Previously Untreated, Suboptimal Advanced Stage Epithelial Ovarian, Primary Peritoneal Cancer, or Fallopian Tube Cancer, Gynecologic Oncology Group ( Philip J. DiSaia ) CDR0000455114, GOG-0218,  ClinicalTrials.gov (NCT00262847)[study is ongoing, but not recruiting participants].

“Decisions Are Made By Those Who Show Up”*

Responding to a threat of a funding reduction to the Department of Defense’s Ovarian Cancer Research Program, during the last week of October the Ovarian Cancer National Alliance urged advocates to contact their Members of Congress to appeal to the Appropriations Defense Subcommittee to increase funding for the research program. As a result of the Ovarian Cancer National Alliance’s advocacy efforts, 14 Senators and 77 Representatives showed their opposition to the funding cut by signing a Dear Colleague letter sent to the Subcommittee Tuesday, November 3, 2009. …

Advocates Work To Prevent Slash In Ovarian Cancer Research Funding

Responding to a threat of a funding reduction to the Department of Defense’s Ovarian Cancer Research Program, during the last week of October the Ovarian Cancer National Alliance (OCNA) urged advocates to contact their Members of Congress to appeal to the Appropriations Defense Subcommittee to increase funding for the research program.

Advocates lobbying on Capitol Hill for increased funds for ovarian cancer research. (Photo: Ovarian Cancer National Alliance)

As a result of OCNA’s advocacy efforts, 14 Senators and 77 Representatives showed their opposition to the funding cut by signing a Dear Colleague letter sent to the Subcommittee Tuesday, November 3, 2009.

The Dear Colleague letter, written by Senator Robert Menendez (D-NJ) and Congresswoman Rosa DeLauro (D-CT), requested that the Subcommittee allocate the $25 million set forth in the U.S. House of Representatives‘ version of the Defense bill, and not the $10 million outlined in the U.S. Senate version of the bill. The Senate funding level represented a 50 percent reduction from the $20 million appropriated in fiscal year (FY) 2009.

The date of the conference subcommittee meeting has yet to be announced.

Established in 1997, the Department of Defense’s Ovarian Cancer Research Program has received $10 million in funding annually from FY 1998 until FY 2008. However, for FY 2009, the program’s funding was doubled to $20 million. The Ovarian Cancer Research Program works to eliminate ovarian cancer by conducting innovative, multidisciplinary research on early detection, screening and treatment of ovarian cancer.

To read the full text of the letter and see if your elected officials signed, please click here.

The Ovarian Cancer Action Network periodically sends out action alerts to notify advocates of pressing issues that need constituent support. To sign up, please click here.

About the Ovarian Cancer National Alliance

OCNA is the advocacy arm of the ovarian cancer movement. OCNA works with federal policy makers, including the  U.S. President, U.S. Congress, and federal agencies like the U.S. Food and Drug Administration (FDA) and the Centers for Medicare and Medicaid Services (CMS). OCNA commits its resources to be a voice for ovarian cancer survivors and significantly reduce the number of deaths from this deadly disease by advocating at the federal level for the following:

• Adequate and sustained funding for ovarian cancer research and awareness programs, and

• Legislation that improves quality of life and access to care for ovarian cancer patients.

Since 1997, when OCNA was founded, death rates from ovarian cancer have not significantly changed. However, OCNA has worked to increase funding for ovarian cancer research, with the goal that this funding will support breakthroughs to help detect ovarian cancer early, treat it more thoroughly, and allow women with ovarian cancer to survive, and thrive.

OCNA has worked to ensure that (i) necessary treatments are covered by Medicare, (ii) drugs and tests on the market are safe and effective, and (iii) federal policy makers are aware of the importance of the ovarian cancer community.

Join OCNA to fight for women with ovarian cancer, and policies that help support them and their families.

Source: Advocates Work To Prevent Slash In Ovarian Cancer Research Funding, News Update, Ovarian Cancer National Alliance, November 11, 2009.

*Title Quote:  Fictional U.S. President Josiah Edward Bartlet, What Kind of Day Has It Been Episode, The West Wing, created by Aaron Sorkin, originally aired May 17, 2000 [Sorkin attributes his teleplay quote to Woody Allen (“80% of success in life is just showing up”)].

FDA Clears Vermillion’s “OVA1” Test To Determine Likelihood of Ovarian Cancer In Women With Pelvic Mass

The U.S. Food and Drug Administration cleared a test that can help detect ovarian cancer in a pelvic mass that is already known to require surgery. The test, called OVA1, helps patients and health care professionals decide what type of surgery should be done and by whom.

First Lab Test That Can Indicate Ovarian Cancer Prior To Biopsy Or Exploratory Surgery

The U.S. Food and Drug Administration (FDA) cleared the OVA1™ Test, the first blood test that, prior to surgery, can help physicians determine if a woman is at risk for a malignant pelvic mass. OVA1 is the first FDA-cleared laboratory test that can indicate the likelihood of ovarian cancer with high sensitivity prior to biopsy or exploratory surgery, even if radiological test results fail to indicate malignancy.

The U.S. Food and Drug Administration (FDA) cleared the OVA1™ Test [formerly, the Ovarian Tumor Triage Test], the first blood test that, prior to surgery, can help physicians determine if a woman is at risk for a malignant pelvic mass. OVA1 is the first FDA-cleared laboratory test that can indicate the likelihood of ovarian cancer with high sensitivity prior to biopsy or exploratory surgery, even if radiological test results fail to indicate malignancy. The test was developed by Vermillion, Inc. (formerly, Ciphergen Biosystems, Inc. ), a molecular diagnostics company, in cooperation with Quest Diagnostics, the world’s leading provider of cancer diagnostics. Quest Diagnostics, which is a long-time investor in research and development of the OVA1 technology, has exclusive rights to offer the test to the clinical reference laboratory market in the U.S. for three years.

“When combined with other clinical information, the OVA1 biomarker panel can help assess the likelihood of malignancy of an ovarian tumor before surgery and facilitate decisions about referral to a gynecologic oncologist,” said Frederick R. Ueland, M.D., principal investigator of the prospective, multi-center OVA1 clinical trial. Dr. Ueland is an associate professor gynecologic oncology at the University of Kentucky‘s Markey Cancer Center.

The OVA1 Test is an in vitro diagnostic multivariate index [assay] (IVDMIA) test that combines the results of five immunoassays using a proprietary unique algorithm to produce a single numerical score indicating a women’s likelihood of malignancy. The OVA1 Test provides a new option in the pre-operative evaluation to help physicians assess if a pelvic mass is benign or malignant in order to help determine whether to refer a woman to a gynecologic oncologist for surgery. Numerous clinical practice guidelines recommend that women with ovarian cancer be under the care of a gynecologic oncologist. However, only an estimated one third of women who undergo surgery for possible ovarian cancer are referred to these specialist surgeons for their surgery.(1)

Vermillion received the Society for Gynecologic Oncologists (SGO) Basic Science Poster Award for an abstract on the performance of its OVA1 Test presented at SGO’s 38th Annual Meeting on Women’s Cancer in 2007. In reviewing the test application, the FDA evaluated results of a prospective, double-blind clinical trial which included 27 demographically mixed sites representative of institutions where ovarian tumor subjects may undergo a gynecological examination.

“Surgery in the hands of a gynecologic oncologist is usually associated with more favorable patient outcomes,” said Jon R. Cohen, M.D., chief medical officer and senior vice president, Quest Diagnostics. “Physicians often do not know if a woman’s pelvic mass is malignant or benign until she undergoes surgery. The OVA1 Test is the first FDA-cleared blood test to help clinicians determine whether to refer a woman to a gynecologic oncologist or have a gynecologic oncologist present at the time of surgery. We believe this test will help drive more favorable patient outcomes.”

“Unfortunately, advances in ovarian cancer diagnosis and treatment are few and far between. It is fitting that September, Ovarian Cancer Awareness Month, marks FDA’s clearance of OVA1, a test that represents an important step forward toward improved outcomes,” said Gail S. Page, executive chairperson of the board of directors of Vermillion. “Quest Diagnostics had the foresight to recognize the potential value of this novel multivariate assay and supported its development. We look forward to collaborating to bring this new diagnostic option to the many women who will benefit from specialist care.”

"When combined with other clinical information, the OVA1 biomarker panel can help assess the likelihood of malignancy of an ovarian tumor before surgery and facilitate decisions about referral to a gynecologic oncologist," said Frederick R. Ueland, M.D., principal investigator of the prospective, multi-center OVA1 clinical trial. Dr. Ueland is an associate professor gynecologic oncology at the University of Kentucky's Markey Cancer Center.

The FDA clearance of OVA1 makes Quest Diagnostics the only diagnostic testing company to offer FDA cleared tests for ovarian cancer in the pre- and post-surgical settings. In addition to offering the OVA1 Test, Quest Diagnostics was the first laboratory company to provide a new lab test that the FDA cleared in the third quarter of 2008 as an aid for monitoring for recurrence of epithelial ovarian cancer.

The OVA1 Test will be available for physician use in the fourth quarter of this year.

Ovarian cancer is the leading cause of death from gynecologic cancers in the United States and the fifth-leading cause of cancer deaths in women.(2) Approximately 21,600 new cases of ovarian cancer will be diagnosed in the U.S. in 2009, and approximately 14,600 women will die of the disease.(3)

About the OVA1 Test

The OVA1 Test is a qualitative serum test that combines the results of five immunoassays into a single numerical score. It is indicated for women who meet the following criteria: over age 18, ovarian adnexal mass present for which surgery is planned, and not yet referred to an oncologist. The test utilizes five well-established biomarkers — Transthyretin (TT or prealbumin), Apolipoprotein A-1 (Apo A-1), Beta2-Microglobulin (Beta2M), Transferrin (Tfr) and Cancer Antigen 125 (CA 125 II) — and a proprietary algorithm to determine the likelihood of malignancy in women with pelvic mass for whom surgery is planned.

The OVA1 Test is an aid to further assess the likelihood that malignancy is present when the physician’s independent clinical and radiological evaluation does not indicate malignancy. The test should not be used without an independent clinical/radiological evaluation and is not intended to be a screening test or to determine whether a patient should proceed to surgery. Incorrect use of the OVA1 Test carries the risk of unnecessary testing, surgery, and/or delayed diagnosis.

About Vermillion

Vermillion, Inc. is dedicated to the discovery, development and commercialization of novel high-value diagnostic tests that help physicians diagnose, treat and improve outcomes for patients. Vermillion, along with its prestigious scientific collaborators, has diagnostic programs in oncology, hematology, cardiology and women’s health. Vermillion is based in Fremont, California. Additional information about Vermillion can be found on the Web at www.vermillion.com.

About Quest Diagnostics

Quest Diagnostics is the world’s leading provider of diagnostic testing, information and services that patients and doctors need to make better healthcare decisions. The company offers the broadest access to diagnostic testing services through its network of laboratories and patient service centers, and provides interpretive consultation through its extensive medical and scientific staff. Quest Diagnostics is a pioneer in developing innovative diagnostic tests and advanced healthcare information technology solutions that help improve patient care. Additional company information is available at www.QuestDiagnostics.com.

(1) Journal of the National Cancer Institute, Vol. 98, No. 3, February 1, 2006

(2) Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin. 2000;50(1):7-33

(3) 2009 American Cancer Society [Leading Sites of New Cancer Cases and Deaths—2009 Estimates]

Contacts:
Quest Diagnostics:
Media: Wendy Bost 973-520-2800
Investors: Kathleen Valentine 973-520-2900

Vermillion:
Jill Totenberg, he Totenberg Group Tel: 212 994 7363
jtotenberg@totenberggroup.com

Select FDA Comments:

The U.S. Food and Drug Administration today cleared a test that can help detect ovarian cancer in a pelvic mass that is already known to require surgery. The test, called OVA1, helps patients and health care professionals decide what type of surgery should be done and by whom.

OVA1 identifies some women who will benefit from referral to a gynecological oncologist for their surgery, despite negative results from other clinical and radiographic tests for ovarian cancer. If other test results suggest cancer, referral to an oncologist is appropriate even with a negative OVA1 result.

OVA1 should be used by primary care physicians or gynecologists as an adjunctive test to complement, not replace, other diagnostic and clinical procedures.

OVA1 uses a blood sample to test for levels of five proteins that change due to ovarian cancer. The test combines the five separate results into a single numerical score between 0 and 10 to indicate the likelihood that the pelvic mass is benign or malignant.

OVA1 is intended only for women, 18 years and older, who are already selected for surgery because of their pelvic mass. It is not intended for ovarian cancer screening or for a definitive diagnosis of ovarian cancer. Interpreting the test result requires knowledge of whether the woman is pre- or post-menopausal.

Sources:

• U.S. Food and Drug Administration Clears Vermillion’s OVA1(TM) Test to Determine Likelihood of Ovarian Cancer in Women with Pelvic Mass – First lab test that can indicate ovarian cancer prior to biopsy or exploratory surgery, Investor Relations, News Release, Vermillion Inc., 11 Sept. 2009.

• FDA Clears a Test for Ovarian Cancer – Test can help identify potential malignancies, guide surgical decisions, News & Events, News Release, U.S. Food & Drug Administration, 11 Sept. 2009.

To Fight Cancer, Know The Enemy

An Op-Ed entitled “To Fight Cancer, Know the Enemy” was published in The New York Times on August 6, 2009.  The author of the Op-Ed was James D. Watson, Ph.D.  James Watson co-discovered the DNA double helix structure; a discovery for which he received the 1962 Nobel Prize for Physiology or Medicine. In the article, Watson states his belief that beating cancer is now a realistic ambition, and he makes several suggestions designed to ensure that victory.

On August 6, 2009, an Op-Ed entitled To Fight Cancer, Know the Enemy was published in The New York Times (NYT).  The author of the article was James D. Watson, Ph.D. James Watson co-discovered the DNA double helix structure; a discovery for which he received the 1962 Nobel Prize for Physiology or Medicine.  Dr. Watson is the Chancellor Emeritus of Cold Spring Harbor Laboratory, and is generally considered the father of molecular biology. Throughout most of his career, James Watson’s novel scientific ideas generated great controversy among, and resistance from, many members of the scientific community.  The suggestions posed by James Watson in his August 6th NYT Op-Ed are likely no exception.

Watson begins the Op-Ed by suggesting an ambitious, yet optimistic, goal in the area of cancer research:

“The National Cancer Institute, which has overseen American efforts on researching and combating cancers since 1971, should take on an ambitious new goal for the next decade:  the development of new drugs that will provide lifelong cures for many, if not all, major cancers.  Beating cancer now is a realistic ambition because, at long last, we largely know its true genetic and chemical characteristics. …”

James D. Watson, Ph.D. is the Chancellor Emeritus of the world-renowned Cold Spring Harbor Laboratory. Dr. Watson co-discovered DNA's double helix structure; a discovery for which he received the 1962 Nobel Prize for Physiology or Medicine. In an Op-Ed published in the New York Times on August 6, 2009, Dr. Watson states: "...Beating cancer now is a realistic ambition because, at long last, we largely know its true genetic and chemical characteristics."

Despite President Nixon’s declaration of  war on cancer in 1971, Watson states that the goal of “beating cancer” was not possible prior to the year 2000, because researchers did not possess the necessary scientific understanding of cancer molecular biology. Extensive details about specific cancers only became known after the 2003 completion of the Human Genome Project, says Watson. Researchers have identified most of the major cellular pathways through which cancer-inducing signals move through cells, and Watson notes that 20 or so signal-blocking drugs are in human clinical testing. By way of example, Watson highlights the breast cancer drug Herceptin, which is used to fight an aggressive form of breast cancer. Herceptin was approved initially by the U.S. Food & Drug Administration (FDA) in 1998, and today represents the standard of care in treating so-called “HER-2 positive” breast cancer.

With this scientific background, Dr. Watson outlines several suggested changes to the current U.S. cancer research paradigm. He believes that the various changes listed below will give the nation a fighting chance to win the war on cancer.

Change FDA Regulations To Allow Combination Testing of New Cancer Drugs Which Are Ineffective As Monotherapies.

Noting the lack of new cancer drugs that lead to lifelong cures, Watson explains that there are many types of cancer-causing “genetic drivers” within a single cancer cell. Although an analysis of several cancer genetic drivers may allow a doctor to prescribe more personalized chemotherapy treatments for the patient, Watson believes that use of drugs against one genetic cancer driver would simply lead to the emergence of increasingly destructive second and third drivers due to the inherent genetic instability of cancer cells.  Accordingly, Watson concludes that most anticancer drugs will not reach their full potential unless they are given in combination to shut down multiple cancer genetic drivers within a cancer cell simultaneously.

Dr. Watson, however, is quick to note that current FDA regulations effectively prohibit combination testing of new cancer drugs that, when administered alone, prove ineffective.  Thus, Watson concludes that current FDA regulations must be amended to allow combination testing of new cancer drugs that prove ineffective as monotherapies.

Better Understand The Chemical (Rather Than Genetic) Makeup of Cancer Cells

Dr. Watson believes that researchers should shift the current focus of cancer research away from decoding the genetic characteristics of cancer, and obtain a better understanding of the chemical reactions that occur within cancer cells. This suggestion, Watson explains, is based upon a 1924 discovery made by the German biochemist (and 1931 Nobel Laureate) Otto Warburg.  During experimentation, Warburg observed that cancer cells, irrespective of whether they grow in the presence or absence of oxygen, produce large amounts of lactic acid. Approximately one year ago, the significance of Warburg’s observation was revealed, says Watson. The metabolism of all proliferating cells (including cancer cells) is largely directed toward the synthesis of cellular building blocks from the breakdown of glucose. Based upon this recent discovery, Dr. Watson concludes that glucose breakdown runs faster in growing cells then in differentiated cells (i.e., cells that stop growing and perform specialized functions within the body).

The turbocharged breakdown of glucose in growing cells is attributable to growth-promoting signal molecules that effectively turn up the levels of transporter proteins which move glucose molecules into the cell, explains Watson. With this important discovery in hand, Watson suggests that researchers determine whether new drugs that specifically inhibit the key enzymes involved in the breakdown of glucose can produce an anticancer effect. Because this determination requires a better understanding of the chemical makeup of cancer cells, Watson believes that biochemists (rather than molecular biologists) will again move to the forefront of cancer research.

NCI Should Fund Smaller Biotechnology Companies & Increase Its Funding to Major Research-Oriented Cancer Centers

The next issue addressed by Dr. Watson relates to the lack of funding available to small biotechnology companies, which are generally engaged in highly innovative research. In the past, the requisite funding of these companies was provided by venture capitalists (VCs), Watson notes.  The level of VC funding required by small biotech companies is not currently available due to the severe U.S. economic downturn. To resolve this critical capital funding issue, Watson suggests that the National Cancer Institute (NCI) fund small biotech companies. This action, Watson believes, will allow the biotech companies to move drug discoveries from the laboratory into human clinical testing on an accelerated basis. In tandem with funding small biotech companies, Dr. Watson also requests NCI to increase its funding to major research-oriented cancer centers that engage in “low probability-high payoff” research projects, which are generally turned down by large pharmaceutical and biotech companies.

President Obama Should Appoint A Strong Leader To The Directorship of NCI

In 1971, the U.S. Congress provided the president, rather than the head of the National Institutes of Health, with the authority to appoint the NCI director.  Watson characterizes NCI in his Op-Ed as “an outpost of the White House” that has “… become a largely rudderless ship in dire need of a bold captain who will settle only for total victory.”  To resolve this issue, Dr. Watson advises President Barack Obama to appoint a strong leader, from among the nation’s best cancer researchers, to the directorship of NCI.  As part of this new leadership structure, Watson also recommends that NCI recruit a seasoned pharmaceutical developer who can radically increase the speed of anticancer drug development and human clinical testing.

Application Of Sun Tzu’s Strategies On The Art Of War To Cancer Research

A statue of the iconic Chinese military leader Sun Tzu. Sun Tzu wrote the earliest -- and still the most revered -- military treatise in the world. This 6th century BC masterpiece is best known to most of us as "The Art of War."

At the conclusion of his Op-Ed, Watson acknowledges that his views will provoke rebuttals from prominent scientists who believe that it is not the right time to wage war on cancer. Moreover, Watson anticipates that many scientists will recommend that, until victory is more certain, the U.S. should not expend large sums of money on cancer research. Watson admits that money alone will not win the war on cancer, but he emphasizes that victory over cancer will not come ” from biding our time.” As part of the Op-Ed title, Watson uses the phrase “know the enemy;” a phrase commonly attributed to the ancient Chinese military leader Sun Tzu. Sun Tzu wrote the earliest — and still the most revered — military treatise in the world.  This 6th century BC masterpiece is best known to most of us as The Art of War.  The clever use of the phrase “know the enemy” by Dr. Watson may suggest that the enemy is indeed cancer, and perhaps, ourselves as represented by the current U.S. cancer research paradigm.

In chapter III of The Art of War, entitled Attack by Stratagem, Sun Tzu describes the dual knowledge that one must possess to achieve ultimate victory in war:

“…If you know the enemy and know yourself, you need not fear the result of a hundred battles. If you know yourself but not the enemy, for every victory gained you will also suffer a defeat. If you know neither the enemy nor yourself, you will succumb in every battle. …”

To follow the advice of James Watson is to better know ourselves and the formidable enemy known as “cancer.” Will Watson’s advice allow us to achieve ultimate victory in the war on cancer? Perhaps. Only time (and appropriate research funding) will tell.

Source: To Fight Cancer, Know The Enemy, by James D. Watson, Op-Ed, The New York Times, August 6, 2009.

FDA Issues Final Rules to Help Patients Gain Access to Investigational Drugs

The U.S. Food and Drug Administration (FDA) published two rules [on August 12, 2009] …that seek to clarify the methods available to seriously ill patients interested in gaining access to investigational drugs and biologics when they are not eligible to participate in a clinical trial and don’t have other satisfactory treatment options.

U.S. Food & Drug Administration

The U.S. Food and Drug Administration (FDA) published two rules [on August 12, 2009] …that seek to clarify the methods available to seriously ill

Margaret A. Hamburg, M.D., Commissioner of Food & Drugs, U.S. Food & Drug Administration

patients interested in gaining access to investigational drugs and biologics when they are not eligible to participate in a clinical trial and don’t have other satisfactory treatment options.

To support the effort to help these patients, the agency also is launching a new Web site where patients and their health care professionals can learn about options for investigational drugs. In general, these options include being treated with a drug that has been approved by FDA, being given an investigational drug as part of a clinical trial, or obtaining access to an investigational drug outside of a clinical trial.

The new rule, “Expanded Access to Investigational Drugs for Treatment Use,” makes investigational drugs more widely available to patients by clarifying procedures and standards. The other rule, “Charging for Investigational Drugs Under an Investigational New Drug Application,” clarifies the specific circumstances and the types of costs for which a manufacturer can charge patients for an investigational drug when used as part of a clinical trial or when used outside the scope of a clinical trial.

“With these initiatives, patients will have the information they need to help them decide whether to seek investigational products,” said Margaret A. Hamburg, M.D., Commissioner of Food and Drugs. “For patients seeking expanded access to investigational drugs and biologics, the new rules make the process easier to understand.”

Clinical trials are studies of drugs and biologics that are still in development and have not yet been approved by the FDA. Many patients enroll in clinical trials to gain access to investigational therapies and contribute to finding out how well an investigational therapy works, and how safe it is for patients. Obtaining a drug or biologic under an expanded access program may be an option for some patients who are not able to enroll in clinical trials.

The FDA has allowed expanded access to experimental drugs and biologics since the 1970s. That access has allowed tens of thousands of patients with HIV/AIDS, cancer, and other conditions to receive promising therapies when no approved alternative is available.

“The final rules balance access to promising new therapies against the need to protect patient safety and seek to ensure that expanded access does not discourage participation in clinical trials or otherwise interfere with the drug development process,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “Clinical trials are the most important part of the drug development process in determining whether new drugs are safe and effective, and how to best use them.”

Source: FDA Issues Final Rules to Help Patients Gain Access to Investigational Drugs, FDA News Release, News & Events, U.S. Food & Drug Administration, 12 Aug. 09.

Additional Information:

• Access To Investigational Drugs, For Consumers, U.S. Food & Drug Administration, 08 Aug. 09.

• Final Rules for Expanded Access to Investigational Drugs for Treatment Use and Charging for Investigational Drugs, U.S. Food & Drug Administration, 13 Aug. 09

FDA Grants Paclical “Orphan Drug” Designation

“Oasmia Pharmaceutical, Uppsala, Sweden, has been granted Orphan Drug designation by the USA FDA of Paclical® for the treatment of ovarian cancer. Orphan Drug designation can entail additional assistance from FDA to expedite and optimize drug development and upon approval a seven year market exclusivity is granted. …”

“Oasmia: FDA grants Paclical® Orphan Drug Designation for ovarian cancer in the USA

Julian Aleksov, CEO, Oasmia Pharmaceutical AB

Oasmia Pharmaceutical, Uppsala, Sweden, has been granted Orphan Drug designation by the USA FDA of Paclical® for the treatment of ovarian cancer. Orphan Drug designation can entail additional assistance from FDA to expedite and optimize drug development and upon approval a seven year market exclusivity is granted.

Orphan drug designation is intended to support the clinical development of new drugs in diseases affecting less than 200,000 people. This provides Oasmia with seven year market exclusivity on the indication when the pharmaceutical is approved. There is no direct generic competition during the period and FDA often provides technical and financial assistance to expedite and optimize drug development.

The designation is based on the hypothesis that Paclitaxel is safer than Taxol®. Oasmia Pharmaceutical is conducting a Phase III study comparing the use of Paclical to Taxol® in patients with ovarian cancer. A safety objective is to show the superiority of hypersensitivity reactions.

This designation shows that the FDA has a great confidence in the company and our product. The United States is one of the most important markets for Paclical®. This decision improves the possibilities for the product, says Julian Aleksov, CEO of Oasmia in a comment.

About Ovarian Cancer
Ovarian cancer is a disease with few and unspecific symptoms at its early stages, and is difficult to detect. The numbers of patients that are diagnosed are increasing on a yearly basis. Ovarian cancer is most often diagnosed in women over 50 years of age, but younger women are also affected. The annual incidence of new diagnosed cases is approximately 125,000 women in EU [European Union] alone. In the USA ovarian cancer accounts for 3 % of all cancer cases and is the fifth leading cause of cancer related deaths in the US.

About Paclical®
With the retinoid based unique platform XR-17, Oasmia has managed to produce a water soluble formulation of Paclitaxel (Paclical®), that does not require premedication and without the severe Cremophor® EL related side effects. The main indication is ovarian cancer. Other planned indications are malignant melanoma and lung cancer (NSCLC).

About Oasmia
Oasmia Pharmaceutical AB develops second and third generation cancer drugs based on nanotechnology for human and veterinary use. The broad portfolio is focused on oncology and contains several promising products in clinical and pre-clinical phase. Oasmia cooperates with leading universities and other biotech companies to discover and optimize substances with a favourable safety profile and better efficacy. The company was founded in 1998 and is based in Uppsala, Sweden. …”

Source: Oasmia: FDA grants Paclical® Orphan Drug Designation for ovarian cancer in the USA, Oasmia Pharmaceutical AB, April 14, 2009.

PhRMA Report Shows Record Number of Development Drugs to Treat Cancer; 63 Ovarian Cancer & 203 Solid Tumor Drugs Listed

“Responding to President Obama’s call for ‘a cure for cancer in our time,’ the Pharmaceutical Research and Manufacturers of America (PhRMA) delivered a new report today on medicines in the research pipeline for cancer. The report shows that America’s pharmaceutical research and biotechnology companies are testing a record 861 new cancer medicines and vaccines. The medicines listed in the report are being tested in human clinical trials or are awaiting approval by the U.S. Food and Drug Administration. [Libby’s H*O*P*E*™ : 63 Ovarian Cancer Drugs & 203 Solid Tumor Drugs are listed in the 2009 PhRMA report (pp. 51 – 55)]. …”

“New Report Shows Record Number of Medicines In Development to Treat Leading Causes of Cancer

Denver, CO (April 1, 2009) – Responding to President Obama’s call for ‘a cure for cancer in our time,’ the Pharmaceutical Research and Manufacturers of America (PhRMA) delivered a new report today on medicines in the research pipeline for cancer. The report shows that America’s pharmaceutical research and biotechnology companies are testing a record 861 new cancer medicines and vaccines. The medicines listed in the report are being tested in human clinical trials or are awaiting approval by the U.S. Food and Drug Administration. [Libby’s H*O*P*E*™ Note: 63 Ovarian Cancer Drugs & 203 Solid Tumor Drugs are listed in the 2009 PhRMA report (pp. 51-55)].

Nationwide, cancer is the second leading cause of death, affecting more than 10 million Americans, according to the National Cancer Institute. This year, more than half a million Americans are expected to die of cancer-more than 1,500 a day. In Colorado, the lifetime risk of cancer is 1 in 2 for males and 2 in 5 for females. The most commonly diagnosed cancer in the state is breast cancer, followed by prostate and lung cancer.

‘We released this report in Denver because of Colorado’s growing role in developing cancer medicines,’ said PhRMA Senior Vice President Ken Johnson, who unveiled the report at the State Capitol Building.

‘Oncology is one of Colorado’s core research competencies, so the President’s call to cure cancer resonates powerfully in our state,’ said Colorado Lt. Governor Barbara O’Brien. ‘We are proud that the cancer medicines now in the research pipeline in Colorado are contributing substantially to the incredible progress made in the last five years by biopharmaceutical companies in developing new and more effective cancer treatments. The nation must continue its strong commitment to the cutting-edge pharmaceutical research that will enable cancer patients to live longer, healthier, and more productive lives.’

Billy Tauzin, President and Chief Executive Officer, The Pharmaceutical Research and Manufacturers of America (PhRMA). PhRMA's mission is to conduct effective advocacy for public policies that encourage discovery of important new medicines for patients by pharmaceutical & biotechnology research companies.

‘I am one of those patients who was diagnosed with cancer and was given a new treatment that brought me from the brink of death back to life,’ says PhRMA President and CEO Billy Tauzin. ‘The men and women working for America’s pharmaceutical research companies are committed to developing new cancer medicines that, one day, could eradicate cancer all together.’

Cancer medicines being developed include 122 for lung cancer, the leading cause of cancer death in the United States; 107 for breast cancer, which is expected to strike more than 180,000 American women this year; 70 for colorectal cancer, which is the third most common cancer in both men and women; and 103 for prostate cancer, which this year is expected to kill 28,000 American men. Additional medicines target brain cancer, kidney cancer, ovarian cancer, pancreatic cancer, skin cancer, and others.

The medicines represent many cutting-edge approaches, including a drug that delivers a synthetic version of a substance derived from scorpions directly to brain tumor cells; a number of cancer vaccines; medicines that target and kill specific cancer cells; and treatments that activate the patient’s general immune system to destroy cancer.

‘Researchers are making exciting progress in the search for new cures and treatments for cancer. But these efforts are wasted if the medicines we develop aren’t accessible to patients who need them,’ said Johnson.

Help is available to patients in need through the Partnership for Prescription Assistance (PPA), a program sponsored by America’s pharmaceutical research companies. To date, the PPA has helped more than 5.7 million patients nationwide, including more than 72,000 people in Colorado. Since its launch in April 2005, the PPA bus tour has visited all 50 states and more than 2,500 cities to educate people about patient assistance programs.

The “Help is Here Express” is staffed by trained specialists able to quickly help uninsured and financially struggling patients access information on more than 475 patient assistance programs, including nearly 200 programs offered by pharmaceutical companies. When the “Help is Here Express” moves on, patients can visit PPA’s easy-to-use Web site (www.pparx.org) or call the toll-free phone number (1-888-4PPA-NOW).

Click here to read Medicines in Development for Cancer 2009. [Adobe Reader PDF Doc.]

Read the backgrounder fact sheet here.

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Pharmaceutical Research & Manufacturers of America

The Pharmaceutical Research and Manufacturers of America (PhRMA) represents the country’s leading pharmaceutical research and biotechnology companies, which are devoted to inventing medicines that allow patients to live longer, healthier, and more productive lives. PhRMA companies are leading the way in the search for new cures. PhRMA members alone invested an estimated $50.3 billion in 2008 in discovering and developing new medicines. Industry-wide research and investment reached a record $65.2 billion in 2008.

PhRMA Internet Address: www.phrma.org

For information on stories of hope and survival, visit: http://sharingmiracles.com/

PhRMA en Español: www.nuestraphrma.org

For information on how innovative medicines save lives, visit: www.innovation.org

For information on the Partnership for Prescription Assistance, visit: www.pparx.org

For information on the danger of imported drugs, visit: www.buysafedrugs.info”

Source:  New Report Shows Record Number of Medicines In Development to Treat Leading Causes of Cancer, Press Release, Pharmaceutical Research and Manufacturers of America, April 1, 2009.

Senators Kennedy & Hutchison Renew War On Cancer

On March 26, 2009, Senators Edward M. Kennedy (D-Massachusetts) and Kay Bailey Hutchison (R-Texas) introduced the 21st Century Cancer Access to Life-Saving Early detection, Research and Treatment (ALERT) Act, a bill to comprehensively address the challenges our nation faces in battling cancer. This is the first sweeping cancer legislation introduced since the National Cancer Act in 1971, authored by Senator Kennedy. The 21^st Century Cancer ALERT Act is a comprehensive approach to cancer prevention and detection, research and treatment. It invests in cancer research infrastructure and improves collaboration among existing efforts. Prevention and early detection for those most at risk are emphasized through support for innovative initiatives and new technologies such as biomarkers.  The legislation addresses the need to increase enrollment in clinical research by increasing access and removing barriers to patients’ participation in clinical trials. The bill also includes a plan designed to improve care for cancer survivors. Additional provisions regarding prevention and screening initiatives will increase access to care for underserved populations and reduce the burden of disease and cost of healthcare to the nation.

Edward M. Kennedy, U.S. Senator For The Commonwealth of Massachusetts

On March 26, 2009, Senators Edward M. Kennedy (D-Massachusetts) and Kay Bailey Hutchison (R-Texas) introduced the 21st Century Cancer Access to Life-Saving Early detection, Research and Treatment (ALERT) Act, a bill to comprehensively address the challenges our nation faces in battling cancer. This is the first sweeping cancer legislation introduced since the National Cancer Act in 1971, authored by Senator Kennedy. The 21^st Century Cancer ALERT Act is a comprehensive approach to cancer prevention and detection, research and treatment. It invests in cancer research infrastructure and improves collaboration among existing efforts. Prevention and early detection for those most at risk are emphasized through support for innovative initiatives and new technologies such as biomarkers.  The legislation addresses the need to increase enrollment in clinical research by increasing access and removing barriers to patients’ participation in clinical trials. The bill also includes a plan designed to improve care for cancer survivors. Additional provisions regarding prevention and screening initiatives will increase access to care for underserved populations and reduce the burden of disease and cost of healthcare to the nation.

We provide below the full text of the following documents:

• Kennedy On The Introduction of the 21st Century ALERT Act, As Entered Into the Congressional Record, Office of Senator Edward M. Kennedy, U.S. Senator For Massachusetts, March 26, 2009.

• Kennedy Renews the War Against Cancer, Press Release, Office of Senator Edward M. Kennedy, U.S. Senator For Massachusetts, March 26, 2009.

• 21st Century Cancer ALERT Act, Senators Kennedy and Hutchinson, Section by Section Summary, Office of Senator Edward M. Kennedy, U.S. Senator For Massachusetts, March 26, 2009.

• Renewing the War on Cancer, by Edward M. Kennedy and Kay Bailey Hutchinson, Op-Ed., Houston Chronicle, March 26, 2009.

• S. 717: 21st Century Cancer ALERT (Access to Life-Saving Early detection, Research and Treatment) Act, 111th Congress,www.govtrack.us (Full text of bill as of April 13, 2009).  CLICK HERE for Adobe Reader PDF document.

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KENNEDY ON THE INTRODUCTION OF THE 21st Century ALERT Act

As Entered into the [Congressional] Record

March 26, 2009

FOR IMMEDIATE RELEASE

Thirty seven years ago, a Republican President and Democratic Congress came together in a new commitment to find a cure for cancer. At the time, a cancer diagnosis meant almost certain death. In 1971, we took action against this deadly disease and passed the National Cancer Act with broad bipartisan support, and it marked the beginning of the War on Cancer.

Since then, significant progress has been made. Amazing scientific research has led to methods to prevent cancer, and treatments that give us more beneficial and humane ways to deal with the illness. The discoveries of basic research, the use of large scale clinical trials, the development of new drugs, and the special focus on prevention and early detection have led to breakthroughs unimaginable only a generation ago.

As a result, cancer today is no longer the automatic death sentence that it was when the war began. But despite the advances we have made against cancer, other changes such as aging of the population, emerging environmental issues, and unhealthy behavior, have allowed cancer to persist. The lives of vast numbers of Americans have been touched by the disease. In 2008, over 1.4 million Americans were diagnosed with some form of cancer, and more than half a million lost their lives to the disease.

The solution isn’t easy but there are steps we can and must take now, if we hope to see the diagnosis rate decline substantially and the survival rate increase in the years ahead. The immediate challenge we face is to reduce the barriers that obstruct progress in cancer research and treatment by integrating our current fragmented and piecemeal system of addressing the disease.

Last year, my colleague Senator Hutchison and I agreed that to build on what the nation has accomplished, we must launch a new and more urgent war on cancer. The 21st Century Cancer ALERT Act we are introducing today will accelerate our progress by using a better approach to fighting this relentless disease. Our goal is to break down the many barriers that impede cancer research and prevent patients from obtaining the treatment that can save their lives.

We must do more to prevent cancer, by emphasizing scientifically proven methods such as tobacco cessation, healthy eating, and exercise. Healthy families and communities that have access to nutritious foods and high quality preventive health care will be our best defense against the disease. I’m confident that swift action on national health reform will make our vision of a healthier nation a reality. Obviously, we cannot prevent all cancers, so it is also essential that the cancers that do arise be diagnosed at an initial, curable stage, with all Americans receiving the best possible care to achieve that goal.

We cannot overemphasize the value of the rigorous scientific efforts that have produced the progress we have made so far. To enhance these efforts, our bill invests in two key aspects of cancer research– infrastructure and collaboration of the researchers. We include programs that will bring resources to the types of cancer we least understand. We invest in scientists who are committed to translating basic research into clinical practice, so that new knowledge will be brought to the patients who will most benefit from it.

One of the most promising new breakthroughs is in identifying and monitoring the biomarkers that leave enough evidence in the body to alert clinicians to subtle signs that cancer may be developing. Biomarkers are the new frontier for improving the lives of cancer patients because they can lead to the earliest possible detection of cancer, and the Cancer ALERT Act will support the development of this revolutionary biomarker technology.

In addition, we give new focus to clinical trials, which have been the cornerstones of our progress in treating cancer in recent decades. Only through clinical trials are we able to discover which treatments truly work. Today, however, less than 5% of cancer patients currently are enrolled in clinical trials, because of the many barriers exist that prevent both providers and patients from participating in these trials. A primary goal of our bill is to begin removing these barriers and expanding access to clinical trials for many more patients.

Further, since many cancer survivors are now living longer lives, our health systems must be able to accommodate these men and women who are successfully fighting against this deadly disease. It’s imperative for health professionals to have the support they need to care for these survivors. To bring good lifelong care to cancer survivors, we must invest more in research to understand the later effects of cancer and how treatments affect survivors’ health and the quality of their lives.

We stand today on the threshold of unprecedented new advances in this era of extraordinary discoveries in the life sciences, especially in personalized medicine, early diagnosis of cancer at the molecular level, and astonishing new treatments based on a patient’s own DNA. To make the remarkable promise of this new era a reality, we must make sure that patients can take DNA tests, free of the fear that their genetic information will somehow be used to discriminate against them. We took a major step toward unlocking the potential of this new era by approving strong protections against genetic discrimination in health insurance and employment when the Genetic Nondiscrimination Act was signed into law last year.

In sum, we need a new model for research, prevention and treatment of cancer, and we are here today to start that debate in Congress. We must move from a magic bullet approach to a broad mosaic of care, in which survivorship is also a key part of our approach to cancer. By doing so, we can take a giant step toward reducing or even eliminating the burden of cancer in our nation and the world. It’s no longer an impossible dream, but a real possibility for the future.

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Press Contact

Anthony Coley/ Melissa Wagoner (202) 224-2633

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Kennedy Renews the War Against Cancer

March 26, 2009

FOR IMMEDIATE RELEASE

Bill will Renew America’s Commitment to Fighting Cancer and Finding Cures

WASHINGTON, DC— Senators Edward M. Kennedy and Kay Bailey Hutchison today introduced the 21st Century Cancer Access to Life-Saving Early detection, Research and Treatment (ALERT) Act, a bill to comprehensively address the challenges our nation faces in battling this disease. This is the first sweeping cancer legislation introduced since the National Cancer Act in 1971, authored by Kennedy.

The 21st Century Cancer ALERT Act will provide critical funding for promising research in early detection, and supply grants for screening and referrals for treatment. These measures will also ensure patient access to prevention and early detection, which is supplemented by increased access to clinical trials and information.

The bill places an emphasis on strengthening cancer research and the urgent need for resources to both prevent and detect cancers at an early stage. The bill strives to give scientists the tools they need to fight cancer and to understand more thoroughly how the disease works. Through fostering new treatments, increased preventative measures and funding for research, the ALERT Act begins a new chapter in how Americans will live with and fight cancer.

Senators Kennedy and Hutchison first proposed the idea for comprehensive cancer legislation last May, when the Health, Education, Labor and Pensions Committee held a hearing to discuss the need for a renewed focus on the deadly disease. Elizabeth Edwards, Lance Armstrong and Hala Moddelmog from Susan G. Komen for the Cure testified at the hearing.

Senator Kennedy, Chairman of the Health, Education, Labor, and Pensions Committee, said, “We’ve come a long way in fighting cancer since we passed the National Cancer Act thirty-eight years ago, but not far enough. Americans still live in fear that they or someone they love will be affected. Today, we’re better equipped for the fight— learning each and every day a little bit more about the disease and what we can do to fight it. Cancer is a complex disease and it requires comprehensive strategies to fight it— strategies that integrate research, prevention and treatment. This bill will renew our efforts to make progress in the battle against cancer, and to give patients and their families a renewed sense of hope.”

“Our nation declared the War on Cancer in 1971, yet, nearly 38 years later, cancer is expected to become the leading killer of Americans. We must bring renewed focus and vigor to this fight.” said Senator Hutchison. “The prescription isn’t simple, but there are steps we must take if we are going to see the cancer diagnosis rate decline, while raising the prognosis for survival among those who do have the disease. Our legislation will enact those necessary steps so we may see more progress and coordination in cancer research and treatment.”

“We know how to lengthen and improve the lives of people with cancer, but we’ve chosen as a nation to turn our backs on some of us who have the disease,” said Elizabeth Edwards. “I urge the United States Senate to embrace the ALERT Act and get it to the President’s desk as soon as possible.”

“In 2010, cancer is expected to be the leading cause of death worldwide. Every American is touched by this disease,” said Lance Armstrong, chairman and founder of the Lance Armstrong Foundation. “The 21st Century Cancer ALERT Act and its authors’ leadership in reforming our nation’s approach to the war on cancer are a very welcome step forward to every member of the LIVESTRONG movement.”

“It’s been 38 years since our nation first declared war on cancer, and yet we are still facing a significant cancer crisis.  The Kennedy-Hutchison Cancer ALERT Act will reignite the war on cancer,” said Nancy G. Brinker, founder of Susan G. Komen for the Cure.  “We must all work together and let nothing stand in the way of discovering and delivering the cures to cancer.”

Senate action on this bill is expected this Congressional session.

A section-by-section summary of the legislation is below as well as an op-ed authored by Senators Hutchison and Kennedy that appeared this morning in the Houston Chronicle and on the Boston Globe’s website.

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21^st Century Cancer ALERT Act

Senators Kennedy and Hutchison

Section by Section Summary

The 21^st Century Cancer ALERT Act is a comprehensive approach to cancer prevention and detection, research and treatment. It invests in cancer research infrastructure and improves collaboration among existing efforts. Prevention and early detection for those most at risk are emphasized through support for innovative initiatives and new technologies such as biomarkers.  The legislation addresses the need to increase enrollment in clinical research by increasing access and removing barriers to patients’ participation in clinical trials. The bill also includes a plan designed to improve care for cancer survivors. Additional provisions regarding prevention and screening initiatives will increase access to care for underserved populations and reduce the burden of disease and cost of healthcare to the nation.

Section 1 and 2 – Findings and Declaration of Purpose

Section 3- Advancement of the National Cancer Program (NCP)

Modernize the role of the National Cancer Institute (NCI) in coordinating the NCP

• Identifies relevant federal agencies to coordinate with NCI
• Improves the annual budget estimate for the NCP by including the needs of the entire NCP and submitting the budget annually to House and Senate Budget and Appropriations Committees
• Increases participation of other federal agencies in the National Cancer Advisory Board
• Encourages early detection and translational research opportunities

Biological Resource Coordination and Advancement of Technologies for Cancer Research

• Establishes an entity within NCI to support an interconnected network of biorepositories with consistent, interoperable systems for collection, storage, annotation, and information sharing
• Facilitates research by linking cancer registries to other federal data sources including those at Centers for Medicare and Medicaid Services [CMS], Social Security Administration, and Centers for Disease Control and Prevention
• Requires hospitals and ambulatory care centers that receive federal funds to offer patients the opportunity to contribute their biospecimens and clinical data to a clinical registry

Section 4 – Comprehensive and Responsible Access to Research, Data, and Outcomes

• Calls for guidance from the Office of Human Research Protection on the use of a centralized Institutional Review Board
• Improves privacy standards in clinical research by clarifying when de-identified patient information may be disclosed
• Calls for HHS to study the advantages and disadvantages of the synchronization of the standards for research under the Common Rule and the Privacy Rule
• Clarifies the application of the Privacy Rule to external researchers

Section 5- Enhanced Focus and Reporting on Cancer Research

• Calls for NCI to report annually on plans and progress regarding research on cancers with low incidence and low survival rates
• Establishes grants program to conduct research on cancers with low incidence and low survival rates

Section 6 – Continuing Access to Care for Prevention and Early Detection

Screening and Early Detection

• Establishes a grant program to states for colorectal cancer screening and referrals for medical treatment (similar to the national breast and cervical cancer early detection program). States are given the option to cover screened persons found to have cancer under Medicaid.

Cancer Prevention

• Authorizes grants for a medical mobile van program to conduct cancer screening and prevention education activities in communities that are underserved and suffer from barriers to preventative cancer care

Access to Prevention and Early Detection for Certain Cancers

• Calls for the Secretary to include cancers with especially low survival rates in the Cancer Genome Atlas Consortium
• Calls for the Secretary to establish formal working groups for cancers with especially low survival rates in the Early Detection Research Network
• Calls for the National Institute of Biomedical Imaging and Bioengineering to ensure that the Quantum Grant program and the Image Guided Interventions program expedite the development of interventions for cancers with low survival rates

Section 7– Early Recognition and Treatment of Cancer Through the Use of Biomarkers

Promote the Discovery and Development of Biomarkers

• Establishes and coordinates federal agencies to establish a highly directed, contract based program that will support the development of innovative biomarker discovery technologies
• Calls for FDA and CMS to work together to create guidelines for clinical study designs that will enable sponsors to generate clinical data that will be adequate for review by both agencies
• Conducts a demonstration project to provide limited regional coverage for biomarker tests and establish procedures for independent research entities to conduct high quality assessments of the efficacy and cost effectiveness of biomarker tests

Section 8: National Cancer Coverage Guidelines

Ensure Patient Access to Clinical Trials

• Facilitates expanded access to clinical trials by requiring ERISA governed health plans to continue to provide coverage of routine care regardless of whether a patient enrolls in a clinical trial

Section 9: Health Professions Workforce

Ensure a Stable Workforce for the Future

• Supports retired nurse military officers to work as nurse faculty
• Directs Secretary of Health and Human Services to identify oncology workforce gaps

Section 10: Patient Navigator Program

Improve Upon Existing Patient Navigator Programs

• Ensures that patient navigators meet minimum core proficiencies
• Reauthorizes the Patient Navigator program through 2015

Section 11: Cancer Care and Coverage Under Medicaid and Medicare

Improvements in Coverage of Cancer Services

• Codifies current Medicare policy to reimburse for routine care while patients are enrolled in clinical trials
• Conducts a demonstration project to evaluate the cost, effectiveness, and potential savings to Medicare of reimbursing providers for comprehensive cancer care planning services to the Medicare population
• Directs states to offer tobacco cessation medications and counseling to pregnant women enrolled in Medicaid

Section 12: Cancer Survivorship and Complete Recovery Initiatives

Childhood Cancers

• Establishes priority areas for NIH activities related to childhood cancer survivorship
• Authorizes grants for research on the causes of health disparities in childhood cancer survivorship and to evaluate follow up care for childhood cancer survivors

Complete Recovery Care

• Defines “complete recovery care” which includes care to address secondary effects of cancer and its treatment, including late and psychosocial effects
• Coordinates complete recovery care activities across federal agencies
• Establishes a Collaborative that will develop a plan for workforce development for complete recovery care

Section 13: Activities of the Food and Drug Administration

Sense of the Senate

• Encourages the FDA to harmonize policies to facilitate the development of drugs; explore clinical trial endpoints; and, modernize the Office of Oncology Drug Products

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Renewing the War on Cancer

By Edward M. Kennedy and Kay Bailey Hutchison

Kay Bailey Hutchison, U.S. Senator For State of Texas

Cancer is a relentless disease. It doesn’t discriminate between men and women, wealthy or poor, the elderly or the young. In 2008, over 1.4 million Americans were diagnosed with some form of the disease. If it wasn’t you, it may have been a spouse or sibling, a parent or a child, a friend or a coworker. We, too, have known the challenges of cancer diagnoses for ourselves or our family members or friends. And while there are many stories of survival, this disease still takes far too many lives. More than half a million Americans lost their battle with cancer last year.

Since the War on Cancer was declared in 1971, we have amassed a wealth of knowledge about the disease. Advances in basic and clinical research have improved treatments significantly. Some of the most important progress has been made in prevention and early detection, particularly screening, including mammography and colonoscopy. Behavior modifications, such as smoking cessation, better eating habits, regular exercise, and sunscreen have been found to prevent many cancers. Continued focus must be placed on prevention, which will always be the best cure.

Though heightened awareness and prevention should be emphasized, alone they don’t translate into adequate progress for those with cancer. Since 1971, the cancer mortality rate has decreased by only 6 percent. In the same period, by contrast, mortality rates have dramatically declined for heart disease (by 56 percent) and stroke (by 66 percent). Today, cancer is the second leading cause of death in the United States, exceeded only by heart disease. If the current trend continues, the National Cancer Institute predicts that one in every two men and one in every three women will be diagnosed with cancer in their lifetimes, and that cancer will become the leading killer of Americans.

The solution isn’t easy, but there are steps we should take now if we hope to see the diagnosis rate decline substantially and the survival rate increase.  To do so, we must identify and remove the numerous barriers that obstruct our progress in cancer research and treatment.

First, it is essential that cancer be diagnosed at an initial, curable stage. One of the most promising breakthroughs is the monitoring of biomarkers, which leave evidence within the body that alerts clinicians to hidden activity indicating that cancer may be developing. Identification of such biomarkers can lead to the earliest possible detection of cancer in patients.

Second, even if we significantly improve early detection, lack of health insurance and other impediments to care will preclude many Americans from undergoing routine screening. With early screening, the disease may be detected at a treatable stage and dramatically increase the rate of survival. Greater outreach is clearly needed to make screening more available to all, and especially to underserved populations.

Third, we must adopt a more coordinated approach to cancer research. Establishing an interconnected network of biorepositories with broadly accessible sources of tissue collection and storage will enable investigators to share information and samples much more effectively. Integrated research will help accelerate the progress of lifesaving research. The search for cures should also be a cooperative goal. The current culture of isolated career research must yield to more cooperative arrangements to expedite breakthroughs. Our national policy should encourage all stakeholders in the War on Cancer to become allies and work in concert toward cures.

Fourth, as our nation’s best and brightest researchers seek new ways to eradicate cancer, we must improve treatment for those who have it today. Raising awareness of clinical trials would result in more patients and their doctors knowing what promising trials are available. Doing so will expand treatment options for patients, and enable researchers to develop better methods for prevention, diagnosis, and therapy.  Today, less than five percent of the 10 million adults with cancer in the United States participate in clinical trials. Disincentives by the health insurance market, preventing patients from enrolling in clinical trials, must be eliminated.

Finally, as our knowledge of cancer advances and patients live longer, we need a process that will improve patient survivorship through comprehensive care planning services. There is great value in equipping patients with a treatment plan and summary of their care when they first enter remission, in order to achieve continuity of therapy and preventing costly, duplicative, or unnecessary services.

We have introduced bipartisan legislation to bring about these necessary changes, and we hope to see the bill enacted in the coming weeks and months. These policy initiatives cannot be fully implemented without broad support and sufficient resources, and we are committed to leading this effort to completion.

It’s time to reinvigorate the War on Cancer, and more effective coordination of policy and science is indispensible for rapid progress.

FDA Issues a Warning Letter to LabCorp Regarding The Illegal Marketing of The OvaSure™ Test

On September 29, 2008, the U.S. Food and Drug Administration (FDA) Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD), Center for Devices and Radiological Health, issued a warning letter (FDA Warning Letter) to the Chief Executive Officer of the Laboratory Corporation of America (LabCorp) regarding the illegal marketing of the OvaSure™ ovarian cancer early detection diagnostic test. …Steven Gutman, M.D., M.B.A., the OIVD Director, informed David P. King, President and Chief Executive Officer of LabCorp, that his company was in serious violation of the Food, Drug, and Cosmetic Act (FDCA) involving the illegal marketing of the OvaSure^TM test and asked that the violations be promptly corrected to avoid initiation of regulatory action by the FDA.

On September 29, 2008, the U.S. Food and Drug Administration (FDA), Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD), Center for Devices and Radiological Health, issued a warning letter (the FDA Warning Letter) to the Chief Executive Officer of the Laboratory Corporation of America (LabCorp) regarding the illegal marketing of the OvaSure™ ovarian cancer early detection diagnostic test.

In the September 29th FDA Warning Letter, Steven Gutman, M.D., M.B.A., the OIVD Director, informed David P. King, President and Chief Executive Officer of LabCorp, that his company was in serious violation of the Food, Drug, and Cosmetic Act (FDCA) involving the illegal marketing of the OvaSure^TM test and asked that the violations be promptly corrected to avoid initiation of regulatory action by the FDA. The FDA Warning Letter was issued to LapCorp after review of information obtained from LabCorp’s website including a press release and a technical bulletin, as well as information provided by LabCorp in a face-to-face meeting with the FDA on September 5, 2008.

The FDA Warning Letter to LapCorp states that the OvaSure™ test is a “device” under the FDCA because it is intended for use in the diagnosis of disease or other conditions, or in the cure, treatment, prevention, or mitigation of disease. Once classified as a “device” under the FDCA (assuming non-applicability of select exemption criteria), LapCorp is required by law to obtain marketing approval or clearance for the OvaSure™ test from the FDA prior to its sale to the public. This FDA finding, in theory, helps protect the public health by ensuring that new devices are shown to be both safe and effective or substantially equivalent to other devices already legally marketed in this country for which approval is not required.

Based upon OIVD’s findings, the FDA concluded that LapCorp did not obtain FDA marketing approval or clearance for the OvaSure™ test and is in violation of Federal law. Specifically, the FDA describes LapCorp’s violations of, and the required corrective action under, the FDCA as follows:

“… The device [i.e., OvaSure™] is adulterated under section 501(f)(1)(B) of the [Food, Drug, and Cosmetic] Act, 21 U.S.C. 351(f)(1)(B), because you do not have an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. 360e(a), or an approved application for an investigational device exemption (IDE) under section 520(g) of the Act, 21 U.S.C. 360j(g). The device is also misbranded under section 502(o) [of] the Act, 21 U.S.C. 352(o), because you did not notify the agency [i.e., the FDA] of your intent to introduce the device into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C. 360(k). For a product requiring premarket approval before marketing, the notification required by section 510(k) of the act is deemed to be satisfied when a premarket approval application (PMA) is pending before the agency. 21 CFR §807.81(b). …

… You should take prompt action to correct these violations. Failure to promptly correct these violations may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties.”

The FDA Warning Letter provides LapCorp with 15 working days to correct its violations under the FDCA as noted above, and to explain how such violations will be prevented in the future. The FDA requests LapCorp to notify the agency if such corrective action cannot be taken within the specified 15 working day time frame.

Libby’s H*O*P*E*™ covered the initial marketing release of LabCorp’s OvaSure™ test and the FDA’s initial inquiry into the clinical validation support underlying the marketing of that test on June 23, 2008 and August 23, 2008, respectively.

Source: FDA Issued a Warning Letter to the CEO of LabCorp Regarding The Illegal Marketing of The OvaSure^TM Test, Office of In Vitro Diagnostic Device Evaluation and Safety, Center for Devices and Radiological Health, Food and Drug Administration. September 29, 2008.

Lost In Translation? FDA Believes That LabCorp’s Ovarian Cancer Early Detection Test (OvaSure) Lacks Adequate Clinical Validation

The U.S. Food and Drug Administration (FDA) sent a letter to the Laboratory Corporation of America (LabCorp) on August 7, 2008, stating that it believes the Yale ovarian cancer early detection test (marketed by LabCorp under the name OvaSure™) ” … has not received adequate clinical validation, and may harm the public health.” In that letter, the FDA invites LabCorp to discuss all validation studies that support the marketing of the OvaSure™ test.

The U.S. Food and Drug Administration (FDA) sent a letter to the Laboratory Corporation of America (LabCorp) on August 7, 2008, stating that it believes the Yale ovarian cancer early detection test (marketed by LabCorp under the name OvaSure™) “… has not received adequate clinical validation, and may harm the public health.” In the letter, the FDA invites LabCorp to discuss all validation studies that support the marketing of the OvaSure™ test. The August 7 FDA letter appears to reflect a previously announced, yet controversial, change in FDA policy. Libby’s H*O*P*E*™ reported previously on the development of the Yale ovarian cancer early detection test [March 14, 2008], and LabCorp’s subsequent market release of that test under the name OvaSure™ [June 23, 2008].

On August 19, 2008, the Oncology STAT™ news service reported that the August 7 FDA letter was posted on the website of the Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD) on August 15, but was removed from the site a few days later. On August 22, 2008, we identified the “cached” copy of the August 7 FDA letter on the OIVD website. The August 7 FDA letter is provided below in its entirety.

The August 7 FDA letter was issued by OIVD and informs LabCorp that “[i]t appears that you are marketing the Ovasure™ Test with performance characteristics (specifically, 95.3% sensitivity and 99.4% specificity) that are identical to those reported in a research study published by Visintin, I. et al., in the February 15 edition of Clinical Cancer Research (Visintin, I. et al., Clin Cancer Res. 2008 Feb 15;14(4):1065-72.).” The OIVD Director, Steven Gutman, M.D., M.B.A., states that the Visintin, I. et. al ” … research was carried out, and performance derived, on two populations that are strongly clinically biased for being healthy and normal, and for having already experienced ovarian cancer.” Based upon this rationale, the OIVD concludes that it does not believe “… the scientific community would consider the reported study sufficient to establish performance characteristics of a test in high risk women who might have ovarian cancer, i.e., in a clinical setting, as claimed in your intended use and promotional materials.”

Historical FDA Policy Regarding Laboratory-Developed (“Home Brew”) Tests

Based upon historical FDA policy, LapCorp would not be required to obtain FDA premarket or postmarket approval for the OvaSure™ test because the early detection test would be categorized as a “laboratory-developed test” (also referred to as a “home brew” test) under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). In general, the CLIA establishes quality standards for all laboratory testing to ensure the accuracy, reliability and timeliness of patient test results regardless of where the test is performed.

Prior to 2006, the FDA did not exercise its authority to regulate home brew tests, which are developed by a laboratory for in-house use as a test service. The reasons are likely twofold. First, the FDA believed that the regulatory oversight exercised by the Centers for Medicare & Medicaid Services (CMS) with respect to the laboratories (under CMS jurisdiction pursuant to CLIA), ensured that such laboratories were competent to properly manufacture and use home brew tests without additional FDA intervention. Second, the FDA possessed regulatory authority to review the primary ingredients or components in the home-brew tests (known as “analyte specific reagents” (ASRs)), and did not believe that further test regulation was necessary.

Announcement of FDA Policy Change For Select In Vitro Diagnostic Assays

In 2006, and again in 2007, the FDA issued draft guidance (entitled, Draft Guidance for Industry, Clinical Laboratories, and FDA Staff: In Vitro Diagnostic Multivariate Index Assays) in which, for the first time, the agency exercised its authority to regulate select in vitro diagnostic multivariate index assays (“IVDMIAs”) that are developed and manufactured by clinical laboratories for their own use (i.e., laboratory-developed tests/home brew tests). An IVDMIA is a diagnostic laboratory assay or test that utilizes mathematical formulae to interpret genetic and protein data required for the generation of information used to make critical diagnosis and treatment decisions for patients. IVDMIAs, for FDA regulatory purposes, are classified as medical devices under the Federal Food, Drug & Cosmetic Act (FDCA), and therefore, can be subject to premarket and postmarket regulation. IVDMIAs developed and manufactured by commercial, non-laboratory-based companies are currently regulated by the FDA. The majority of IVDMIAs, however, are developed and manufactured by laboratories for their own use as home brew tests.

Under the FDA draft guidance, home brew IVDMIAs would in many cases require 510(k) pre-market clearance or Pre-Market Approval (PMA). In addition, these same IVDMIAs would have to comply with “device” post-market manufacturing and reporting requirements. The August 7 FDA letter does not state that a 510(k) pre-market clearance or Pre-Market Approval is required; rather OIVD invites LabCorp to discuss any “validation strategies” undertaken beyond the research results reported by Visintin, I. et. al. LabCorp is not the only company affected by the FDA policy change. The FDA also used its change in regulatory policy to prevent Correlogic Systems, Inc. from marketing its ovarian cancer early detection test, known as OvaCheck®, without prior FDA approval. Arguably, the FDA is placing the OvaSure™ and OvaCheck® ovarian cancer early detection tests on equal regulatory footing.

Ever-Increasing Sophistication of Genetic and Proteomic Assay Technology

The emergence and increased use of IVDMIAs using novel technology (e.g., proteomics) as an integral part of patient diagnosis and treatment, and their direct advertisement to consumers, may have influenced the FDA to conclude more recently that the current level of oversight with respect to genetic and proteomic testing by laboratories was inadequate. Assuming the FDA position is correct, inadequate federal oversight could lead to significant issues related to the quality and validity of IVDMIAs.

LabCorp Amendment of OvaSure™ “Use” Information

LabCorp recently amended its intended use and promotional materials to provide that the OvaSure™ test cannot be used by a woman who has had both ovaries removed (i.e., a woman who previously had a bilateral oophorectomy). Specifically, LabCorp intends that the OvaSure™ test be used to identify a woman who is at “high-risk” for ovarian cancer; however, an ovarian cancer survivor who is currently in remission, cannot use the OvaSure™ test to screen for a recurrence of the disease if her ovaries were removed as part of her first-line treatment after the initial ovarian cancer diagnosis. CLICK HERE to view Libby’s H*O*P*E* post (with updates) dated June 23, 2008, regarding the OvaSure™ test use and limitation information as amended.

Letter to the President and Chief Executive Officer of LabCorp

August 7, 2008
Via FedEx

David P. King
President and Chief Executive Officer
Laboratory Corporation of America
430 South Spring Street
Burlington, North Carolina 27215

Dear Mr. King:

It has come to our attention that you are currently marketing the OvaSure™ Yale Ovarian Cancer Test, also advertised as the OvaSure™ For Women at High-Risk for Ovarian Cancer, and OvaSure™ For Women at High-Risk for Ovarian Cancer, (Serial Monitor), (collectively referred to hereafter as the OvaSure™ Test) which is intended to be used as a tool to identify high-risk women who might have ovarian carcinoma. It appears that you are marketing the OvaSure™ Test with performance characteristics (specifically, 95.3% sensitivity and 99.4% specificity) that are identical to those reported in a research study published by Visintin, I., et al., in the February 15 edition of Clinical Cancer Research (Visintin, I. et al., Clin Cancer Res. 2008 Feb 15;14(4):1065-72.). We note that this research was carried out, and performance derived, on two populations that are strongly clinically biased for being healthy and normal, and for having already experienced ovarian cancer. Based on the available information, we do not believe the scientific community would consider the reported study sufficient to establish performance characteristics of a test in high risk women who might have ovarian cancer, i.e., in a clinical setting, as claimed in your intended use and promotional materials.

Based on our review of your promotional materials and the research publication cited above, we believe you are offering a high risk test that has not received adequate clinical validation, and may harm the public health. We would like to discuss with you your offer of this test, and any validation strategies you have undertaken beyond those reported in the publication cited above.

We look forward to discussing this with you, and are committed to working with you as we strive to protect the public health without unnecessarily imposing regulatory burdens on the marketing of products of potential clinical importance.

Sincerely yours,

/S/

Steven I. Gutman, M.D., M.B.A.
Office Director
Office of In Vitro Diagnostic Device Evaluation and Safety
Center for Devices and Radiological Health

Comments:

• The corporate and governmental intrigue surrounding the FDA regulatory issues with respect to the OvaSure™ and OvaCheck® ovarian cancer early detection tests would make for a thrilling Hollywood screenplay, except for the catastrophic fact that approximately 15,000 U.S. women die annually from ovarian cancer due to the lack of a reliable early detection test. Because of the latter, approximately 80 percent of women are not diagnosed until they are in advance stages of the disease.

• The FDA’s current – and still evolving – policy signals a strong possibility that previously unregulated diagnostics could require FDA approval or clearance prior to marketing as well as being subject to other medical device requirements under the FDCA.

• It is critical for the FDA to take whatever action is necessary to protect U.S. public health. It is also essential that ovarian cancer survivors, clinicians and all affected corporate entities receive clear, consistent regulatory guidance and prompt action from the FDA with respect to this potential life-saving matter.

Sources:

• FDA Questions LabCorp in Its Ovarian Cancer Test Service, OncologySTAT™ News, Week in Review, Issue 33, Aug. 22, 2008 (reprinting article by D. Filmore, The Pink Sheet Daily, Aug. 19, 2008).
• Draft Guidance for Industry,Clinical Laboratories, and FDA Staff: In Vitro Diagnostic Multivariate Index Assays, July 26, 2007 (Adobe Reader PDF doc.)
• Office of In Vitro Diagnostic Device Evaluation & Safety, Centers For Devices and Radiological Health, U.S. Food & Drug Administration (online).
• Clinical Laboratory Improvement Amendments (CLIA) (online), Centers for Medicare & Medicaid Services, U.S. Department of Health & Human Services.
• CLIA-Clinical Laboratory Improvement Amendments (online), Center For Devices and Radiological Health, U.S. Food & Drug Administration
• Clinical Proteomics Advances as Vermillion, LabCorp, Correlogic Prep For Market, by Bernadette Toner, ProteoMonitor, June 26, 2008 (online version)
• Recent U.S. Regulatory Developments Herald Increasing FDA Regulation of Laboratory-Developed Diagnostic Tests and Services, by Jane E. Baluss, The Pulse publication, Foley & Lardner LLP, October 5, 2007.
• Significant extension of FDA regulatory oversight over certain “home brew” laboratory tests, by Jill Alvarez & Teresa Kelto, FDA Alert (a publication of Nixon Peabody LLP), Sept. 25, 2006.

Updates:

• August 25, 2008: Cancer Test For Women Raises Hope, and Concern, by Andrew Pollack, Health Section (online edition), The New York Times, Aug. 25, 2008 (Aug. 26, p. F1. NY print edition).

• September 9, 2008: The FDA recently reposted on its website, a copy of the August 7th letter to the President and Chief Executive Officer of LabCorp regarding OvaSure™. To view a copy of the letter, CLICK HERE.

• October 8, 2008: FDA Issues A Warning Letter to LabCorp Regarding The Illegal Marketing of the OvaSure™ Test, by Paul Cacciatore, Libby’s H*O*P*E*, Oct. 8, 2008.

Increased Worldwide Focus on the Safety of Drugs Used To Treat Chemotherapy-Related Anemia

Over the past month, there was considerable press coverage regarding the safety and proper use of epoetin alfa (marketed as Epogen® & Procrit®) and darbepoetin (marketed as Aranesp®). Both drugs are erythropoiesis-stimulating agents (ESAs).

This controvery began between December 2006 and February 2007, when the U.S. Food and Drug Administration (FDA) was made aware of several studies in cancer patients that showed higher mortality or shorter time to tumor progression in patients randomized to receive an ESA as compared to placebo. Some of the trials dosed patients in the ESA treatment group to achieve hemoglobin levels ≥ 12 g/dl (higher than recommended on the ESAs drug box labeling). Other trials included anemic patients who were not on chemotherapy or radiotherapy. These studies were discussed at a May 10, 2007 meeting of the Oncology Drug Advisory Committee of the FDA (ODAC). The ODAC recommended additional restrictions in the labeling for ESAs including: (i) specific tumor types for which adverse safety signals were observed with the use of an ESA, (ii) instructions for hemoglobin trigger level-based dose modification/suspension, and (iii) instruction to discontinue use of ESAs upon completion of chemotherapy.

With respect to cancer the FDA recommendations to healthcare professionals include the following:

• ESAs shortened the overall survival and/or time-to-tumor progression in patients with various cancers;

• Risks of shortened survival and tumor progression have not been excluded when ESAs are dosed with the intent to achieve hemoglobin levels <12g/dL;

• Use the lowest dose of [Aranesp/EPOGEN/PROCRIT] needed to avoid red blood cell transfusions. Do not exceed the upper safety limit for hemoglobin levels of 12 g/dL;

• Reduce the ESA dose by 25% when hemoglobin reaches a level needed to avoid transfusion;

• Withhold dosing with an ESA when hemoglobin level exceeds 12 g/dL;

• Restart dosing at 25% below the previous dose when the hemoglobin approaches a level where transfusions may be required;

• Use ESAs only for the treatment of anemia due to concomitant myelosuppressive chemotherapy;

• Discontinue treatment with an ESA following the completion of a course of chemotherapy; and

• Use of ESAs in cancer patients have not been demonstrated in controlled clinical trials to improve the symptoms of anemia, quality of life, fatigue, or well-being.

The FDA also provided patient counseling guidance to healthcare professionals with respect to the use of ESAs. As part of a risk minimization plan, the FDA announced that it is developing a patient “Medication Guide” to better communicate the risks and benefits of ESA use to patients. Physicians and other healthcare professionals were advised by the FDA to discuss the following talking points with their patients:

• The primary goal of treatment with erythropoiesis stimulating agents (ESA) is to increase the number of red blood cells in order to avoid receiving blood transfusions.

• ESAs require at least 2 weeks of treatment before there is an increase in the number of red blood cells and the dose may be adjusted periodically but not more often than every 4 weeks.

• ESAs increase the patient’s chance of blood clots and the risk of dying may be greater in certain circumstances

• Patients should keep appointments for blood tests so hemoglobin levels can be monitored.

• Patients need to monitor their blood pressure and contact their doctor if there are any changes outside of the range that has been established for them.

• Patients should contact their doctor if they experience any of the following symptoms:

o Pain and/or swelling in the legs;
o Worsening in shortness of breath;
o Increases in blood pressure;
o Dizziness or loss of consciousness;
o Extreme tiredness; and
o Blood clots in hemodialysis vascular access ports

On June 26, 2008 -in a surprising announcement – the European Medicines Agency (EMEA) urged oncologists to favor blood transfusions over ESAs. Although these popular drugs have been used to treat cancer-related anemia for close to 20 years and have become a mainstay of therapy, the new recommendation is encouraging clinicians to reverse this common practice. The EMEA committee for Medicinal Products for Human Use (CHMP) recommendation is based upon its review of new data from studies that showed an increased risk for tumor progression, venous thromboembolism, and shorter overall survival in patients who received ESAs. “In cancer patients with a reasonably long life expectancy, the benefit of using epoetins does not outweigh the risk of tumor progression and shorter overall survival,” the committee noted in a statement. There are many U.S. doctors who believe that there is simply not enough data to conclude that ESAs are unsafe. Despite that fact, the ESA controversy is likely to continue until definitive fact-based evidence is fully developed.

Sources:

• Information on Erythropoiesis Stimulating Agents (ESA)(marketed as Procrit, Epogen, and Aranesp), Center For Drug Evaluation and Research, U.S. Food & Drug Administration (website information).
• Questions and Answers On Epoteins and the Risk of Tumour Growth and Blood Clots in the Veins (Adobe PDF Document), European Medicines Agency Press Release, June 26, 2008.
• New Study Probes Safety of Erythropoiesis-Stimulating Agents (Free Registration Required to View), by Allison Gandey, Medscape Medical News, Medscape Today, June 10, 2008 (online article includes two videos).
• European Regulators Say Transfusions Safer Than ESAs in Cancer (Free Registration Required to View), by Allison Gandey, Medscape Medical News, Medscape Today, June 30, 2008.

Vermillion Files FDA Pre-Market Application for OVA1 Ovarian Tumor Triage Test

” …The OVA1 [Ovarian Tumor Triage Test] test will help assess the risk of malignancy in the hundreds of thousands of women who require surgery for ovarian tumors each year. ‘This information can be used to identify those who might benefit from referral to a gynecologic oncologist,’ said Fred Ueland, M.D., principal investigator of the study and Associate Professor of Gynecologic Oncology at the University of Kentucky. While most tumors are benign, numerous studies have shown that women with ovarian cancer have better overall outcomes when their surgery is performed by a gynecologic oncologist.”

“ FREMONT, Calif., June 25 /PRNewswire-FirstCall/ — Vermillion, Inc. (Nasdaq: VRML), a molecular diagnostics company, today announced that it has submitted a 510(k) pre-market notification application to the U.S. Food & Drug Administration (FDA) requesting regulatory clearance of its Ovarian Tumor Triage Test known as OVA1™.

As announced previously, the OVA1 prospective clinical trial met its primary endpoints, indicating that the test is capable of stratifying women with pelvic masses into high- and low-risk categories to help determine whether the patient should be referred to a specialist prior to surgery. The clinical trial was one of the largest ovarian cancer studies ever conducted and assessed more than 550 women with a confirmed adnexal mass at 27 clinical sites in the United States. Additionally, the trial was the culmination of more than eight independent studies in more than 2,500 women.

The OVA1 test will help assess the risk of malignancy in the hundreds of thousands of women who require surgery for ovarian tumors each year. ‘This information can be used to identify those who might benefit from referral to a gynecologic oncologist,’ said Fred Ueland, M.D., principal investigator of the study and Associate Professor of Gynecologic Oncology at the University of Kentucky. While most tumors are benign, numerous studies have shown that women with ovarian cancer have better overall outcomes when their surgery is performed by a gynecologic oncologist.

This is an important milestone for Vermillion and a significant step toward the commercialization of OVA1™. ‘We are pleased with the results of the trial and look forward to discussing the significance of our data and our commercialization strategy in an upcoming investor roundtable, planned for July,’ said Gail Page, President and CEO of Vermillion. ‘We also look forward to receiving regulatory clearance from the FDA and making OVA1 available to the hundreds of thousands of women who could benefit considerably from the test.’

Vermillion will host a roundtable teleconference to address the need for OVA1 on Tuesday, July 15. Fred Ueland, M.D., principal investigator of the OVA1 clinical study, will serve as the keynote speaker. Conference call details, including dial-in information and timing, are forthcoming.

About Vermillion’s Ovarian Cancer Diagnostic Program

In addition to developing a diagnostic test designed to distinguish between benign and malignant pelvic masses, Vermillion has a broad program of ovarian cancer diagnostic tests in development. Studies are underway to validate diagnostic tests developed to detect early-stage ovarian cancer, predict prognosis and recurrence, and identify women considered at high-risk for the disease.

Vermillion’s comprehensive diagnostic development program is being conducted with several leading collaborators at The Johns Hopkins School of Medicine, The University of Texas M.D. Anderson Cancer Center, Rigshospitalet (Copenhagen), and the University of Kentucky.

The Company’s OVA1 test is part of a strategic alliance with Quest Diagnostics to jointly develop and commercialize diagnostic tests.

About Vermillion

Vermillion, Inc. is dedicated to the discovery, development and commercialization of novel high-value diagnostic tests that help physicians diagnose, treat and improve outcomes for patients. Vermillion, along with its prestigious scientific collaborators, has diagnostic programs in oncology, hematology, cardiology and women’s health. Vermillion is based in Fremont, California. Additional information about Vermillion can be found on the Web at http://www.vermillion.com.”

[Quoted Source: Vermillion Files 510(k) Application With U.S. Food & Drug Administration for OVA1 Ovarian Tumor Triage Test – Significant Milestone Achieved Based on Compelling Clinical Studies, Vermillion, Inc. Press Release, June 25, 2008.]

Additional Information:  To learn more about molecular diagnostics and proteomics, see Understanding Cancer Series: Molecular Diagnostics, National Cancer Institute, September 1, 2006.