The US Food and Drug Administration (FDA) has granted Standard Review designation to Onyx Pharmaceuticals Inc's New Drug Application (NDA) for carfilzomib for the potential treatment of patients with relapsed and refractory multiple myeloma. The Prescription Drug User Fee Act (PDUFA) date for completion of review by the FDA of the NDA is July 27, 2012.

In the NDA filing designation letter from the FDA, received December 9th, the agency advised the company that recent Oncology Drug Advisory Committee recommendations specify a preference for phase III trials for the accelerated approval pathway. Based on its preliminary review and ongoing assessment of the application, the FDA outlined potential review issues including whether the application is sufficient to support an FDA conclusion that the data provided within the NDA meets accelerated approval criteria and whether the benefit and risk are appropriately balanced, given that the application is based on a single-arm study.

“Our goal remains to make this promising new therapy available to patients with relapsed and refractory multiple myeloma as quickly as possible,” said Ted W Love, MD, executive vice president, research and development and technical operations at Onyx Pharmaceuticals. “We are committed to working with the agency to address the comments outlined in the letter.”

The submission is based on the 003-A1 study, an open-label, single-arm phase II b trial. The trial evaluated 266 heavily-pretreated patients with relapsed and refractory multiple myeloma who had received at least two prior therapies, including bortezomib and either thalidomide or lenalidomide. Refractory disease was defined as less than or equal to a 25 percent response or progression during therapy, or progression within 60 days after completion of therapy. The primary endpoint was overall response rate. Secondary endpoints included duration of response, clinical benefit rate, overall survival, time-to-progression, progression-free survival, and safety. Safety data from additional carfilzomib studies were also included in the submission. The safety database in the NDA includes 526 patients with multiple myeloma.

Carfilzomib is being studied in several clinical trials either as a single-agent or in combination with other therapies, including:

A phase III clinical trial, known as the ASPIRE trial, is evaluating the combination of lenalidomide and low dose dexamethasone with or without carfilzomib in patients with relapsed multiple myeloma who have received one to three prior therapies. The company has an agreement with the FDA on a Special Protocol Assessment (SPA) on the design and planned analysis of the ASPIRE trial.

A phase III clinical trial, called the FOCUS trial to support registration in Europe, is evaluating single-agent carfilzomib in patients with relapsed and refractory myeloma who have received three or more prior therapies.

A phase I/II study being conducted by Onyx's partner Ono Pharmaceutical Co., Ltd is evaluating carfilzomib in Japanese patients with relapsed/refractory multiple myeloma.

An expanded access program is underway in partnership with the Multiple Myeloma Research Foundation for eligible patients in the US, with relapsed and refractory multiple myeloma for whom no satisfactory treatment alternatives are available.

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. engaged in the development and commercialization of innovative therapies for improving the lives of people with cancer and other serious diseases.