Onyx Pharmaceuticals, Inc. announced positive top-line results from the phase 2b 003-A1 study of single-agent carfilzomib, a selective, next generation proteasome inhibitor, in patients with relapsed and refractory multiple myeloma.

In an independent review of the data, carfilzomib achieved an overall response rate (partial response or greater) of 24 per cent and a median duration of response of 7.4 months in patients who entered the study after receiving a median of five prior lines of therapy (corresponding to a median of 13 anti-myeloma agents) and whose disease was refractory to their last therapeutic regimen. The clinical benefit rate (minimal response or greater) in the study population was 36 per cent. Carfilzomib was well-tolerated and there were no new or unexpected toxicities observed. Full results of the trial will be presented at an upcoming scientific meeting. Based on these results, Onyx is continuing discussions with the US Food and Drug Administration (FDA) regarding next steps in filing a new drug application (NDA) for carfilzomib, which the company expects to submit by year-end 2010 for potential accelerated approval in the US.

"Despite recent advances in treating multiple myeloma, all patients eventually relapse. The unmet medical need remains great, as the outlook for patients with relapsed and refractory disease is grim," said Michael G. Kauffman, M.D., Ph.D., Chief Medical Officer of Onyx Pharmaceuticals. "According to a study from the International Myeloma Working Group, patients, such as those enrolled in the 003-A1 study, can expect to respond to therapy only 11 percent of the time and survive for only six to 10 months.1 The single-agent activity with durable disease control and favorable tolerability observed in this study indicate that carfilzomib has the potential to alter the natural course of this deadly disease."

"Carfilzomib has the potential to be an important therapy in multiple myeloma and exemplifies the Onyx vision to build a leading oncology company by developing innovative targeted therapies," said N. Anthony Coles, M.D., president and chief executive officer of Onyx Pharmaceuticals. "We are committed to bringing this promising treatment to patients as quickly as possible by pursuing an accelerated approval pathway in the US, while simultaneously moving forward with two Phase 3 studies. The first study, ASPIRE, is designed to support full carfilzomib registration in the US in earlier-stage patients who have relapsed following initial lines of therapy, and the second study is designed to support approval in relapsed and refractory patients in Europe."

The 003-A1 study was an open-label, single-arm phase 2b trial. The trial evaluated 266 heavily-pretreated patients with relapsed and refractory multiple myeloma whose disease was refractory to their last treatment regimen and who had received at least two prior therapies, including bortezomib, either thalidomide or lenalidomide, an alkylating agent, glucocorticoids and an anthracycline. Refractory disease was defined as ? 25% response or progression during therapy or within 60 days after completion of therapy.2 Patients enrolled in the 003-A1 trial had received a median of five prior therapeutic regimens, corresponding to a median of 13 anti-myeloma agents. Patients received carfilzomib at 20mg/m2 for the first cycle followed by 27mg/m2 thereafter for up to 12 cycles. Patients who completed the 12 cycles were eligible to enter an extension study. Responses and progression were determined according to the International Myeloma Working Group (IMWG) criteria. The trial was conducted in collaboration with the Multiple Myeloma Research Consortium (MMRC) and at additional sites in the US and Canada.

"The patients in the 003-A1 trial represent an advanced population with significant unmet medical need who had received many lines of therapy and had limited options available to them outside of a clinical trial, strongly underscoring the need for new treatments. We are proud to have worked with the Onyx team that is developing carfilzomib and are encouraged by these results," said Kathy Giusti, Founder and CEO of the MMRC and a multiple myeloma patient. The MMRC initiated a relationship with the company (then Proteolix) in 2006, which included the participation of 11 MMRC Member Institutions in the 003-A1 trial, representing 36 percent of the total trial centers and 60 percent of enrolled patients.

"There is a high unmet need for treatment options for patients with relapsed and refractory multiple myeloma who are no longer responding to available therapies," said Brian G.M. Durie, M.D., Cofounder and Chair of the Board of Directors of the International Myeloma Foundation (IMF).

Carfilzomib is a selective, next-generation proteasome inhibitor that has shown encouraging results in a broad clinical trial program in multiple myeloma.

Onyx Pharmaceuticals, Inc. is a biopharmaceutical company committed to improving the lives of people with cancer. The company, in collaboration with Bayer HealthCare Pharmaceuticals, Inc., 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.