2011 ASCO: EC145 Demonstrates 85 Percent Improvement in Progression-Free Survival for Treatment of Platinum Resistant Ovarian Cancer

EC145, in combination with pegylated liposomal doxorubicin (Doxil®/Caelyx®) in patients with platinum-resistant ovarian cancer, met its primary endpoint by showing an 85 percent (2.3 month) improvement in median progression-free survival in the intent-to-treat population, and a 260 percent (4.0 month) improvement in a subset of folate receptor positive patients. The final EC145 phase 2 clinical study data were presented today at the 2011 American Society of Clinical Oncology Annual Meeting.

EC145 delivers a very potent vinca chemotherapy directly to cancer cells by targeting the folate receptor expressed on cancer cells, but not on most normal cells. Approximately 80-90 percent of ovarian and lung cancers express the receptor, as do many other types of cancer. Click on the picture above to view a video regarding EC145's mechanism of action. (Photo: Endocyte, Inc.)

Endocyte, Inc., a biopharmaceutical company developing targeted small molecule drug conjugates (SMDCs) and companion imaging diagnostics for personalized therapy, today announced that the phase 2 PRECEDENT trial, which is investigating the company’s lead drug candidate, EC145, in combination with pegylated liposomal doxorubicin (PLD)(brand name: Doxil®/Caelyx®) in patients with platinum-resistant ovarian cancer, met its primary endpoint by showing: (i) an 85 percent (2.3 month) improvement in median progression-free survival (PFS) in the intent-to-treat population, and (ii) a 260 percent (4.0 month) improvement in a subset of folate receptor positive patients. EC145 in combination with PLD showed limited additional toxicity compared to standard therapy with PLD alone. The most commonly occurring adverse events were neutropenia, small intestine obstruction, and palmar-plantar erythrodysesthesia (or hand-foot syndrome). EC145 is a therapeutic that targets the folate receptor and EC20 is a companion imaging diagnostic used to assess folate receptor presence.

These final PFS data from the PRECEDENT trial were presented today at the 2011 Annual Meeting of the American Society of Clinical Oncology (ASCO), in Chicago, Illinois and are available at http://investor.endocyte.com/events.cfm.

“I am encouraged by these data as EC145 is the first drug candidate to demonstrate a significant improvement in PFS in a randomized trial of patients with platinum-resistant ovarian cancer, a very challenging disease with a high unmet need. Historical data show that for these patients on standard therapy, PFS is approximately three months and overall survival is approximately twelve months. No new drug has been approved in the U.S. for this indication in over a decade,” said Wendel Naumann, M.D., Associate Director of Gynecologic Oncology at Blumenthal Cancer Center, Carolinas Medical Center. “In addition the companion imaging diagnostic, EC20, is designed to identify patients who over-express the targeted receptor and are most likely to respond to EC145. This represents a personalized therapeutic approach that I believe will help oncologists direct patients to the most promising treatment.”

EC145 Phase 2 PRECEDENT Clinical Study Data 

The Phase 2 PRECEDENT trial was an international, multi-center, randomized study of 149 women with platinum-resistant ovarian cancer. Patients were randomized to receive EC145 plus PLD or PLD alone at a standard dose until disease progression or death. The primary endpoint of the study was progression-free survival. Secondary endpoints included response rate and overall survival.

The EC145 phase 2 PRECEDENT trial results are summarized below.

  • 85 Percent (2.3 Month) Improvement in Median Progression-Free Survival for All Patients

Patients receiving EC145 in combination with PLD, regardless of folate receptor expression, had a median progression free survival of 5.0 months compared to 2.7 months for patients receiving single agent PLD. The hazard ratio for PFS was 0.626 (p=0.031). The overall response rate was 28 percent in the EC145 combination group versus 16 percent in the PLD-alone group. CA-125 (cancer antigen-125) responses were also more common in patients receiving EC145 in combination with PLD compared to those receiving PLD alone, with response rates (based on CA-125 blood serum measurement) of 38 percent and 19 percent, respectively.

  • 260 Percent (4.0 Month) Improvement in Median Progression-Free Survival for Patients Most Positive for Folate Receptor

The study also utilized EC20, an investigational companion imaging diagnostic that is designed to identify patients with folate receptor positive tumors. As expected, in the folate receptor positive patients the improvement in PFS was even greater. In the subpopulation most positive for the folate receptor, PFS increased 4.0 months from 1.5 months to 5.5 months. The hazard ratio for PFS was 0.381 (p=0.018). This represents more than a 60 percent reduction in the risk of progression and provides evidence supporting the mechanism of action through targeting of the folate receptor. The overall response rate was 22 percent in the EC145 combination group versus 7 percent in the PLD alone group. CA-125 responses were also more common in patients receiving EC145 in combination with PLD compared to those receiving PLD alone, 43 percent and 13 percent, respectively.

“We see tremendous potential for continued development of EC145 based on these data that demonstrate, for the first time, a significant improvement in PFS in patients with platinum resistant ovarian cancer,” said Ron Ellis, President and Chief Executive Officer of Endocyte. “We have already advanced EC145 into Phase 3 evaluation with the PROCEED trial, which has a similar design to the PRECEDENT trial, and plan to file for regulatory approval in the European Union based on the PFS data from the PRECEDENT study.”

Plan to File PRECEDENT Data for Conditional Approval in Europe

As a result of Endocyte’s interaction with the European Medicines Agency (EMA), including a meeting with the Scientific Advice Working Party and written advice from the Committee for Medicinal Products for Human Use (CHMP), the Company will prepare marketing applications for both EC145 and EC20. Based on feedback from the CHMP, Endocyte plans to seek conditional marketing authorization for patients with platinum-resistant ovarian cancer who test positive for the folate receptor using the EC20 companion imaging diagnostic.

Phase 3 PROCEED Trial Initiated

Endocyte recently announced the initiation of patient enrollment in the Phase 3 PROCEED trial of EC145, which is structured to replicate the PRECEDENT trial design. The Phase 3 trial is a randomized, double-blinded trial of EC145 in combination with PLD compared to PLD plus placebo. The patient population — those with platinum-resistant ovarian cancer — will be the same as in the PRECEDENT trial, and the primary endpoint will be progression-free survival in patients selected by EC20 as folate-receptor positive. The trial will also be statistically powered for overall survival as a secondary endpoint with projected enrollment in excess of 500 patients. The trial will be conducted in approximately 150 sites in the U.S., Canada, and Europe.  More information regarding the trial is available at www.clinicaltrials.gov.

About EC145

EC145 is a conjugate of the vitamin folate and a super-potent vinca alkaloid. Folate is required for cell division and rapidly dividing cancer cells often over-express folate receptors in order to capture enough folate to support cell division. By attaching a chemotherapy drug to folate through proprietary chemistry, EC145 targets cancer cells while avoiding most normal cells. This targeted approach is designed to provide treatment with super-potent drugs while lowering toxicity compared to standard chemotherapy.

About EC20

EC20 is a folate-targeted molecular imaging agent that is being developed as a non-invasive method to identify tumors that over-express folate receptors. These tumors are the molecular target of Endocyte’s folate-targeted therapeutic compounds such as EC145. To date, EC20 has been administered to over 500 patients and has been found to be well tolerated.

About Endocyte

Endocyte is a biopharmaceutical company developing targeted therapies for the treatment of cancer and inflammatory diseases. Endocyte uses its proprietary technology to create novel small molecule drug conjugates (SMDCs) and companion imaging diagnostics for personalized targeted therapies. The company’s SMDCs actively target receptors that are over-expressed on diseased cells, relative to healthy cells. This targeted approach is designed to enable the treatment of patients with highly active drugs at greater doses, delivered more frequently, and over longer periods of time than would be possible with the untargeted drug alone. The companion imaging diagnostics are designed to identify patients whose disease over-expresses the target of the therapy and who are therefore more likely to benefit from treatment.

Sources:

  • EC145 PRECEDENT Trial Results — 2011 American Society of Clinical Oncology Annual Meeting Poster Presentation, June 5, 2011. [Adobe Reader PDF document]
EC145 PROCEED Clinical Trial Information:
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Endocyte Begins Phase II Clinical Trial of EC145 for Treatment of Women with Platinum Resistant Ovarian Cancer

Endocyte Inc. has announced the initiation of a randomized Phase II clinical study of the company’s investigational drug EC145 in women with platinum-resistant ovarian cancer. The phase II trial, also called the “PRECEDENT study,” will evaluate the efficacy and safety of EC145 when administered in combination with pegylated liposomal doxorubicin (PLD). …The PRECEDENT study will enroll 122 subjects and involve more than 50 clinical centers in the U.S., Canada, and Europe. … EC145 links a very potent anticancer drug to the vitamin folate, which is required for cell division. Rapidly dividing cancer cells over-express folate receptors to capture enough folate to support cell division. By combining a chemotherapy drug with folate, EC145 targets cancer cells while avoiding normal cells. This targeted approach is designed to provide treatment with more potent drugs with lower toxicity.”

″WEST LAFAYETTE, IN. – February 19, 2009 – Endocyte Inc. has announced the initiation of a randomized Phase II clinical study of the company’s investigational drug EC145 in women with platinumresistant ovarian cancer. The phase II trial, also called the “PRECEDENT study,” will evaluate the efficacy and safety of EC145 when administered in combination with pegylated liposomal doxorubicin (PLD).  PLD is widely used as a standard therapy for women with platinum-resistant ovarian cancer. The efficacy and safety of the combination of EC145/PLD  will be compared to treatment with PLD without EC145. Ovarian cancer is the fifth most common cancer among women in the United States and the leading cause of death due to cancer of the female reproductive system. The PRECEDENT study will enroll 122 subjects and involve more than 50 clinical centers in the U.S., Canada, and Europe. Trial details can be found at www.endocyte.com and http://www.clinicaltrials.gov.  EC145 links a very potent anticancer drug to the vitamin folate, which is required for cell division. Rapidly dividing cancer cells over-express folate receptors to capture enough folate to support cell division. By combining a chemotherapy drug with folate, EC145 targets cancer cells while avoiding normal cells. This targeted approach is designed to provide treatment with more potent drugs with lower toxicity.

  Advanced Ovarian Cancer - Imaging folate-receptors cancer cells using EC20 (folate-Tc99m). Source:  Endocyte

Advanced Ovarian Cancer - Imaging folate-receptors cancer cells using EC20 (folate-Tc99m). Source: Endocyte

In addition to EC145, patients in the PRECEDENT trial will also be treated with a new molecular imaging agent called EC20 developed by Endocyte. By targeting folate receptors, EC20 imaging agent allows clinicians to identify tumors that overexpress the folate receptor. Using EC20, doctors may be able to identify, in advance, those patients who will benefit from EC145 therapy. According to Dr. Wendel Naumann of the Blumenthal Cancer Center, Carolinas Medical Center and principal investigator for the PRECEDENT study, ‘Patients with advanced, platinum resistant, ovarian cancer are in need of therapy that does not result in significant toxicity. The earlier clinical studies of EC145 were encouraging because they indicated that clinicians could use EC20 to identify women whose tumors expressed the molecular target of EC145. Therapy with EC145 might benefit these patients without causing significant additional toxicity.’ ‘The start of the PRECEDENT study is another important validation of Endocyte’s promising DGS [Drug Guidance System] technology platform,” said Dr. Richard Messmann, Endocyte’s vice president for medical affairs. ‘This also represents an important milestone in Endocyte’s efforts to develop a range of new drugs and predictive medicine tools to treat cancer and other serious diseases in the years ahead. ‘

About Endocyte
Endocyte is a privately-held biotechnology company with headquarters in the Purdue Research Park of West Lafayette, IN. Based on the applications of Endocyte’s advanced proprietary Drug Guidance System (DGS), the Company is working to develop new drugs and diagnostic agents to treat many types of cancer and other serious diseases. The DGS platform makes it possible to use highly-potent drugs on extended and frequent dosing schedules and in combination with other drugs to maximize efficacy. The technology improves drug targeting and reduces the risk of side effects by combining drugs with ligands that are able to identify and attach to receptors found on tumor and other disease cells. Endocyte is currently conducting three separate Phase 2 clinical trials for its lead compound, EC145, together with EC20, a companion molecular imaging agent, for the treatment of ovarian cancer and non-small cell lung cancer. Other clinical-stage products in the Endocyte pipeline include: EC0225, a combination of two potent anticancer drugs; BMS493, a potent drug being developed in partnership with Bristol-Myers Squibb; EC17, a targeted immunotherapy agent; and EC0489, a targeted cancer drug. The Company also has multiple product candidates in pre-clinical stage development.  This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management’s current expectations and involve significant risks and uncertainties that may cause results to differ materially from those set forth in the statements. We undertake no obligation to publicly update any forwardlooking statement, whether as a result of new information, future events, or otherwise.

Contacts:
Vickey Buskirk, media relations, Endocyte Inc., (765) 463-7175 ext. 1117, vbuskirk@endocyte.com”

Quoted Source: ENDOCYTE BEGINS PHASE II CLINICAL TRIAL OF EC145 FOR TREATMENT OF WOMEN WITH OVARIAN CANCER, News Release, February 19, 2009 (PDF Document).

Other Sources:

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