Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced its plans to expand the Phase 3 European clinical trial FOCUS, which is evaluating the efficacy and tolerability of carfilzomib, a selective next-generation proteasome inhibitor. The FOCUS trial is designed to support the registrational filing with the European Medicines Agency (EMA) in patients with relapsed and refractory myeloma.
The FOCUS (CarFilzOmib for AdvanCed Refractory MUltiple Myeloma European Study) trial modification includes two key enhancements to the study: changing the primary end point to overall survival (OS) from progression-free survival (PFS) and correspondingly increasing patient enrollment to 300 from 84. These modifications are supported by overall survival data from the Phase 2b 003-A1 study evaluating single-agent carfilzomib in patients with relapsed and refractory multiple myeloma announced at the American Society of Hematology (ASH) meeting in December 2010. The company expects to review these data with the EMA and is moving forward with plans to do so.
"Given the encouraging carfilzomib data reported to date, including the 003-A1 survival data, Onyx decided to make this change to demonstrate a potential mortality benefit for carfilzomib," said Ted Love, M.D., executive vice president, research and development and technical operations at Onyx. "We plan to upsize the trial at the currently active sites by leveraging the momentum we are seeing in enrollment as well as by adding additional sites, as appropriate."
Focus Trial Design
As modified, the Phase 3 FOCUS study will be a randomized 300-patient trial evaluating carfilzomib versus best supportive care of low dose steroids plus cytoxan (optional), in patients with relapsed and refractory multiple myeloma following treatment with at least three prior therapies. Patients are being randomized to receive carfilzomib (20mg/m2 on days 1 and 2 of cycle 1 only, then 27mg/m2 subsequently). The primary endpoint is overall survival with secondary endpoints including PFS, overall response rate (ORR), clinical benefit rate (CBR) and duration of response (DOR), as well as safety. The study design incorporates planned interim analyses on the primary endpoint.
Onyx on Track for Submission of NDA in the U.S.
In January, Onyx announced that the U.S. Food and Drug Administration (FDA) had granted fast track designation for carfilzomib. Onyx has initiated a rolling submission of a New Drug Application (NDA) for potential accelerated approval of carfilzomib in the U.S. Through the Fast Track designation, Onyx is eligible to submit the carfilzomib NDA on a rolling basis, allowing Onyx to begin the NDA filing process immediately and giving the FDA an opportunity to review the completed sections of the registration application. Onyx has now submitted the non-clinical section of the carfilzomib NDA with the FDA and commenced its rolling NDA process. Onyx intends to complete its submission of the NDA for potential accelerated approval of carfilzomib in the U.S. as early as mid-2011.
Onyx Pharmaceuticals, Inc.