Ariad Pharmaceuticals, Inc. has reached an agreement with US Food and Drug Administration (FDA) on a special protocol assessment (SPA) for its global phase 3 trial of oral deforolimus in patients with metastatic sarcomas. Based on the SPA, progression-free survival (PFS) will be the primary endpoint of the phase 3 trial, while overall survival will be a secondary endpoint. The company is expected to begin patient enrolment for the trial later this month.
The SPA is a written agreement between the trial's sponsor and FDA regarding the design, endpoints and planned method of conducting and analysing a trial to be used in support of regulatory approval, a company press release said. The European Medicines Agency (EMEA) has provided protocol advice consistent with that of FDA regarding the phase 3 trial design, as part of its protocol assistance program. Ariad and Merck & Co. Inc. have entered into a global collaboration to jointly develop and commercialize deforolimus for use in cancer.
"We are extremely pleased with the outcome of our positive and collaborative discussions with FDA review staff regarding the design of our phase 3 trial for oral deforolimus in metastatic sarcomas. Working with leading sarcoma experts and our clinical investigators, we were able to successfully resolve the open issues regarding the trial's endpoints and reach agreement with the agency on PFS as the primary endpoint," said, Camille Bedrosian, managing director and chief medical officer, Ariad.
Ariad and Merck plans to conduct phase 3 trial for oral deforolimus in patients with metastatic soft-tissue and bone sarcomas following a favourable response to chemotherapy - a period when continued treatment with traditional chemotherapeutic agents has not been established to provide additional clinical benefit.
This double-blind trial is designed to evaluate approximately 650 patients, who will be randomized (1:1) to oral deforolimus or placebo at approximately 125 sites. The trial is 90 per cent powered to detect a 33 per cent increase in median PFS (corresponding to a hazard ratio of 0.75) comparing the oral deforolimus arm with the placebo arm. Two interim analyses are included. Complete patient enrolment and the second interim analysis are expected to take place within two years of the first patient being enrolled.
Pierre F. Dodion, M.D., senior vice president, oncology, Ariad, said, "FDA agreement on our overall phase 3 trial design, patient population and endpoints, as well as our newly established partnership with Merck represent important achievements for the global development of deforolimus."
Ariad's lead product candidate, deforolimus, is a novel small-molecule inhibitor of the protein mTOR, a master switch in cancer cells. Blocking mTOR creates a starvation-like effect in cancer cells by interfering with cell growth, division, metabolism, and angiogenesis. Patient enrolment has been completed in multiple phase 1 and 2 clinical trials of deforolimus in patients with solid tumours and haematological cancers. The global phase 3 trial of oral deforolimus in metastatic soft-tissue and bone sarcomas is the subject of SPA with the U.S. Food and Drug Administration (FDA). Deforolimus has been designated both as a fast-track product and an orphan drug by the FDA and as an orphan drug by the European Medicines Agency for the treatment of sarcomas. Ariad has a global partnership with Merck & Co., Inc. to develop and commercialize deforolimus in multiple cancer indications. Ariad also is collaborating with Medinol Ltd. to develop stents and other medical devices that deliver deforolimus to prevent reblockage at sites of vascular injury following stent-assisted angioplasty.