Onyx Pharmaceuticals, Inc. announced its plans to expand the phase III 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 II b 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, MD, 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.”

As modified, the phase III 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.

In January, Onyx announced that the US 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 US. 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. Now it has submitted the non-clinical section of the carfilzomib NDA with the FDA and commenced its rolling NDA process and intends to complete its submission of the NDA for potential accelerated approval of carfilzomib in the US as early as mid-2011.

The carfilzomib development programme includes a large, randomized international phase III clinical trial, known as the ASPIRE trial, studying the combination of lenalidomide and low dose dexamethasone with or without carfilzomib in patients with relapsed multiple myeloma. The company has an agreement with the US Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) and received Scientific Advice from the European Medicines Agency (EMA) on the design and planned analysis of the ASPIRE trial. Carfilzomib is also being evaluated in a broad investigator sponsored trial program including 1st line multiple myeloma, combination studies, lymphoma and other malignancies.

Multiple myeloma is the second most common haematologic cancer and results from an abnormality of plasma cells, usually in the bone marrow.

Onyx Pharmaceuticals, Inc. is a biopharmaceutical company committed to improving the lives of people with cancer. It is developing and marketing Nexavar (sorafenib) tablets, a small molecule drug that is currently approved for the treatment of liver cancer and advanced kidney cancer with Bayer HealthCare Pharmaceuticals Inc.