Merck and Endocyte announce acceptance for review of European Marketing Authorization applications for vintafolide and companion Diagnostic etarfolatide for folate-receptor positive platinum-resistant ovarian cancer

Merck, known as MSD outside the United States and Canada (NYSE: MRK), and Endocyte Inc. (NASDAQ: ECYT), today announced that the European Medicines Agency (EMA) has accepted for review the marketing authorization application (MAA) filings for the novel investigational cancer candidate vintafolide (MK-8109/EC145) and investigational companion diagnostic imaging agent etarfolatide (EC20), for the targeted treatment of patients with folate-receptor positive platinum-resistant ovarian cancer in combination with pegylated liposomal doxorubicin (PLD). Both vintafolide and etarfolatide have been granted orphan drug status by the European Commission.

Vintafolide is a proprietary, injectable, conjugate consisting of folate (vitamin B9) linked to a potent vinca alkaloid anti-cancer agent, desacetylvinblastine hydrazide (DAVLBH). Folate is essential for cell division, and cancer cells generally consume higher levels of folate than normal cells to fuel their rapid rate of growth and division. In order to satisfy the demand for folate, some cancer cell types – including ovarian – express high concentrations of folate receptors on their surface. Vintafolide is designed to exploit this characteristic by selectively targeting the folate receptor to deliver the anti-cancer agent DAVLBH intracellular to the tumor.

“The acceptance of the EMA filing for vintafolide is an important milestone for Merck and Endocyte,” said Gary Gilliland, M.D., Ph.D., senior vice president and oncology franchise head, Merck Research Laboratories. “Vintafolide is designed to preferentially target cancer cells that actively take up folate via the folate receptor.”

The MAA filings are supported by four clinical studies: a Phase I study in solid tumors, two single-agent, single-arm Phase II studies in ovarian cancer and non-small cell lung cancer, and the PRECEDENT trial, a randomized Phase IIb study in patients with platinum-resistant ovarian cancer. The application is being submitted for conditional approval on the basis that the results from the Phase II studies fulfill an unmet medical need.

Vintafolide is currently being evaluated in a Phase III randomized, double-blind clinical trial for platinum-resistant ovarian cancer (PROCEED trial). The PROCEED trial is evaluating vintafolide in combination with PLD compared to PLD plus placebo for the treatment of folate-receptor positive platinum-resistant ovarian cancer. This trial also employs the companion diagnostic imaging agent etarfolatide, which is a molecular imaging agent that is being developed as a non-invasive method to identify tumors that over-express folate receptors. The primary endpoint of the trial is progression-free survival as measured by RECIST v 1.1 (Response Evaluation Criteria In Solid Tumor) criteria in patients with all target tumor lesions positive as assessed by etarfolatide imaging. Overall survival is a secondary endpoint. The trial anticipates recruiting patients at approximately 150 sites in the United States, Canada, Europe and Asia. For further information regarding these trials, please visit http://www.clinicaltrials.gov.

“We are pleased with the acceptance of the applications in Europe as an important milestone towards providing a new treatment option targeted for folate-receptor positive platinum-resistant ovarian cancer patients,” said Ron Ellis, Endocyte’s president and CEO. “The use of etarfolatide as a companion diagnostic imaging agent to guide patient selection for vintafolide is a key element in implementing a personalized medicine approach to treating ovarian cancer.”

As part of an exclusive license agreement with Endocyte, Merck, through an MSD affiliate, is responsible for the development and worldwide commercialization of vintafolide in oncology. Endocyte intends to co-promote vintafolide in the United States, and is responsible for the development, manufacture and commercialization of etarfolatide worldwide. Merck will pay Endocyte a $5 million milestone payment for the EMA filing acceptance.

About Folate-Receptor Positive Platinum-Resistant Ovarian Cancer

In 2012, it is estimated that there will be 22,280 new cases of ovarian cancer in the United States and over 40,000 new cases in the European Union. Ovarian cancer causes more deaths than any other cancer of the female reproductive system. Overall, approximately 80 percent of patients relapse after first-line platinum-based chemotherapy. Platinum-resistant ovarian cancer is a challenging disease with a high unmet need. This type of cancer recurs within six months of completion with a platinum-containing regimen, the standard of care for ovarian cancer. An estimated 80 percent of platinum-resistant ovarian cancer patients have been found to have folate-receptor positive disease, and 40 percent express the receptor in all of their target tumor lesions. Compared to patients who do not express folate receptors on their tumors, folate-receptor positive patients have been shown to have a poorer overall prognosis.