WEST LAFAYETTE, Ind.—Endocyte Inc. and U.S.-based pharma giant Merck, known as MSD outside the United States and Canada, announced March 21 that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) had issued positive opinions for the Conditional Marketing Authorization of Vynfinit (vintafolide) and the companion imaging agents Folcepri (etarfolatide), and Neocepri (intravenous folic acid), for the treatment of adult patients with folate receptor-positive, platinum-resistant ovarian cancer in combination with pegylated liposomal doxorubicin (PLD).
Endocyte and Merck entered into a vintafolide partnership worth as much as $1 billion in April 2012. Under this partnership, Encodyte granted Merck an exclusive license to develop, manufacture, and commercialize vintafolide, with Endocyte to co-promote vintafolide in the United States upon approval by the U.S. Food and Drug Administration. Endocyte remained responsible for conducting the PROCEED Phase 3 clinical study in women with platinum-resistant ovarian cancer and the TARGET Phase 2b second-line non-small-cell lung cancer study. Merck is responsible for further clinical studies in any other potential indications.
“These positive CHMP opinions bring Merck and Endocyte one step closer to providing a personalized approach to address a significant unmet medical need in platinum-resistant ovarian cancer,” said Dr. Eric Rubin, vice president of clinical development for oncology at Merck Research Laboratories.
“Vintafolide is a folate receptor-targeted agent, and if approved, would be the first oncology therapeutic to employ an imaging agent as a companion diagnostic for patient selection,” noted Ron Ellis, Endocyte's president and CEO, adding the CHMP recommendation is a step that helps “validate our company's focus on the development of targeted medicines and companion imaging agents designed to improve patient outcomes.”
Vintafolide is proposed for use in combination with PLD for the treatment of adult patients with platinum-resistant ovarian cancer who express the folate receptor on all target lesions. Folate receptor status should be assessed by a diagnostic medicinal product approved for the selection of adult patients for treatment with vintafolide, using single-photon emission computed tomography (SPECT) imaging, in combination with computed tomography (CT) or magnetic resonance imaging (MRI).
Etarfolatide and IV folic acid are medicinal products proposed for diagnostic use only. Etarfolatide, following radiolabelling with sodium pertechnetate (99mTc) solution, is proposed for SPECT imaging in combination with CT or MRI, for the selection of adult patients for treatment with vintafolide. Intravenous folic acid would be administrated prior to 99mTc-etarfolatide for the enhancement of SPECT image quality.
The applications for Conditional Marketing Authorisation for vintafolide, etarfolatide and IV folic acid were submitted based on results in platinum-resistant ovarian cancer patients who express the folate receptor on all target lesions as evaluated in the PRECEDENT Phase 2 study.
The CHMP opinion will be reviewed by the European Commission and, if approved, would be granted a centralized marketing authorization with unified labeling that is valid in the 28 countries that are members of the European Union, as well as European Economic Area members Iceland, Liechtenstein and Norway. This process usually completes within three months of a CHMP opinion.
But that wasn’t the only good vintafolide news on March 21, with Endocyte also announcing results from its Phase 2b TARGET trial, which showed that the study met the primary endpoint for the combination of vintafolide and docetaxel in folate receptor-positive recurrent NSCLC patients
The data indicated that risk of disease worsening or death, otherwise known as progression-free survival, was reduced by 25 percent for patients treated with the vintafolide/docetaxel combination versus docetaxel alone. Detailed trial results, including data regarding overall survival, will be presented at an upcoming medical conference.
The TARGET trial was conducted in 199 patients, randomized to one of three arms: vintafolide alone, vintafolide/docetaxel combination, or docetaxel alone. Secondary endpoints, including overall response rate and overall survival, also showed trends in favor of the combination arm. Median overall survival has been reached for the vintafolide and docetaxel single-agent arms but has not yet been reached in the combination arm, according to Endocyte. In addition, the investigational combination regimen showed better activity in patients with adenocarcinoma, a subset analysis prespecified in the trial design.
“This is our second randomized study in a very challenging indication, where vintafolide has met the primary endpoint when used in patients selected with the companion imaging agent etarfolatide,” said Dr. Binh Nguyen, vice president of medical affairs at Endocyte. “These results provide further validation of our targeted approach to treatment using companion imaging and our SMDC technology. We were especially pleased with the results in the adenocarcinoma population and early overall survival trends, and we have learned important information about the dosing schedule.”
Vintafolide (EC145/MK-8109) is said to deliver a potent vinca alkaloid chemotherapy directly to cancer cells by targeting the folate receptor expressed on cancer cells, but not on most normal cells. As noted by Endocyte on its website, some 80 percent to 90 percent of ovarian and lung cancers express the receptor, as do many other types of cancer. In addition to the PROCEED and TARGET trials, vintafolide has also been evaluated in the completed and published PRECEDENT study, a randomized Phase 2 trial comparing vintafolide plus PLD versus PLD alone in women with platinum-resistant ovarian cancer. Vintafolide is also to be evaluated in women with triple-negative breast cancer in a Phase 2b study scheduled to begin this year.
