The U.S. Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC) determined by a vote of 11-0 [with 1 abstention] earlier today, that, in patients with relapsed and refractory multiple myeloma who have received at least two prior lines of therapy that included a proteasome inhibitor and an immunomodulatory agent (IMiD), the benefit-risk assessment is favorable for the use of carfilzomib (proposed brand name Kyprolis?).
Onyx Pharmaceuticals, based in South San Francisco, California, is developing carfilzomib for use in multiple myeloma across a variety of treatment lines.
Multiple myeloma is the second most common hematologic cancer and results from an abnormality of plasma cells, usually in the bone marrow. In the United States, more than 50,000 people are living with multiple myeloma and approximately 20,000 new cases are diagnosed annually.  Worldwide, more than 180,000 people are living with multiple myeloma and approximately 86,000 new cases are diagnosed annually. 
“Today’s ODAC recommendation is an important regulatory milestone in the review of carfilzomib for relapsed and refractory multiple myeloma,” said Ted W. Love, M.D., Executive Vice President, Research and Development and Technical Operations at Onyx Pharmaceuticals.
The Prescription Drug User Fee Act (PDUFA) date for completion of FDA review of the Kyprolis NDA for accelerated approval is July 27, 2012. The ODAC provides FDA with independent expert advice and recommendations, however the final decision regarding approval is made by FDA.
The carfilzomib NDA is based on the 003-A1 study, an open-label, single-arm Phase 2b trial as well as supportive data from additional studies. The 003-A1 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.
Carfilzomib is an investigational agent and is not approved by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) or other health authorities.
Carfilzomib is being studied in several clinical trials either as a single-agent or in combination with other therapies, including:
– A global Phase III clinical trial, known as the ASPIRE trial, has completed enrollment and 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) and has received Scientific Advice from the European Medicines Agency (EMA) on the design and planned analysis of the trial.
– A Phase III clinical trial, called the FOCUS trial, is evaluating single-agent carfilzomib in patients with relapsed and refractory myeloma who have received three or more prior therapies. The trial is designed to facilitate regulatory approvals around the world.
– A global Phase III clinical trial, called ENDEAVOR, is planned to begin enrolling patients in mid-2012. The head-to-head trial will evaluate the combination of carfilzomib and low-dose dexamethasone vs. the combination of bortezomib and low-dose dexamethasone.
– A Phase 1/2 study being conducted by Onyx’s partner Ono Pharmaceutical Co., Ltd is evaluating carfilzomib in Japanese patients with relapsed/refractory multiple myeloma.
 National Cancer Institute, Surveillance Epidemiology and End Results, 2007 Facts and Figures
 International Agency for Research on Cancer, GLOBOCAN 2002 database.