Onyx Pharmaceuticals Initiates a Phase 3 Carfilzomib Combination Trial in Relapsed Multiple Myeloma

EMERYVILLE, Calif., July 21 /PRNewswire-FirstCall/ -- Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced that the company has begun enrollment in the ASPIRE trial, a Phase 3 international clinical trial evaluating carfilzomib in combination with lenalidomide (Revlimid®) and low dose dexamethasone in patients with relapsed multiple myeloma. The company has an agreement with the U.S. 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.

"We have seen encouraging interim results from previous studies of carfilzomib in combination with lenalidomide and dexamethasone, and this Phase 3 trial will further evaluate this promising three-drug combination therapy in patients with relapsed myeloma," said Michael Kauffman, M.D., Ph.D., Chief Medical Officer at Onyx.  "In addition to this Phase 3 study, we look forward to reporting the top-line results from our pivotal Phase 2b single-agent trial in advanced myeloma patients shortly, which may enable us to pursue an accelerated approval strategy in the United States.  Given the promising efficacy signal observed to date for carfilzomib and the potential to combine it with other agents, we believe that carfilzomib may have the opportunity to benefit a broad range of myeloma patients, and we are committed to advancing this compound as quickly as possible."  

Phase 1/2 Study Results

As previously reported at the at the 46th American Society of Clinical Oncology (ASCO) Annual Meeting, a Phase 1/2 dose-escalation trial, known as the 006 study, evaluated carfilzomib in combination with lenalidomide and low dose dexamethasone in patients with relapsed and/or refractory myeloma.  The overall response rate in the cohorts of patients receiving full doses of the combination was 75 percent in 48 evaluable patients. The combination was well tolerated and demonstrated activity, including in patients who had received prior bortezomib (Velcade®) and an IMiD.  No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached.  The maximum per-protocol doses of 27mg/m2 carfilzomib, 25mg lenalidomide, and low dose (40mg) dexamethasone were safely administered.  

Phase 3 Trial Design

Based on the interim results of the 006 study, the company has begun enrollment in a large randomized, international Phase 3 clinical trial, known as the ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma) trial, formerly referred to as the 009 trial.  ASPIRE  is a 700 patient trial evaluating carfilzomib in combination with lenalidomide and low dose dexamethasone, versus lenalidomide and low dose dexamethasone alone, in patients with relapsed multiple myeloma following treatment with one to three prior regimens.  The primary endpoint of the trial is progression-free survival.  Secondary endpoints include overall survival, overall response rate, duration of response, disease control rate, safety, time-to-progression and time-to-next treatment.  Patients will be randomized to receive carfilzomib (20mg/m2 on days 1 and 2 of cycle 1 only, then 27mg/m2 subsequently), in addition to a standard dosing schedule of lenalidomide (25mg per day for 21 days on, 7 days off) and low-dose dexamethasone (40mg per week in 4 week cycles), versus lenalidomide and low-dose dexamethasone alone.

The study will be conducted at approximately 200 sites in North America, Europe, and Israel.  For information about this study, please visit www.clinicaltrials.gov.

About the Carfilzomib Development Program

Carfilzomib is a selective, next-generation proteasome inhibitor that is being investigated in a broad clinical trial program in multiple myeloma.

The pivotal Phase 2b single-agent study, also known as 003-A1, enrolled patients with relapsed/refractory multiple myeloma.  Top-line results, expected in mid-2010, may support the filing of a U.S. New Drug Application (NDA) by year-end 2010.  

A Phase 3 European clinical trial, called FOCUS (CarFilzOmib for AdvanCed Refractory MUltiple Myeloma European Study) and formerly known as the 011 trial, will evaluate carfilzomib in relapsed/refractory myeloma and is designed to support a registrational filing with the EMA. This trial is expected to begin shortly.  Carfilzomib is also being evaluated in advanced solid tumors.

About Multiple Myeloma

Multiple myeloma is the second most common hematologic cancer and results from an abnormality of plasma cells, usually in the bone marrow. In the U.S., more than 50,000 people are living with multiple myeloma and approximately 20,000 new cases are diagnosed annually.(i)  According to estimates by the European Network of Cancer Registries, there are 21,420 new cases of multiple myeloma in Europe each year and around 15,000 deaths from this illness. It is estimated that 60,000 people in Europe are currently living with this disease.

Worldwide, more than 180,000 people are living with multiple myeloma and approximately 86,000 new cases are diagnosed annually.(ii)

About Onyx Pharmaceuticals, Inc.

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. Additionally, Nexavar is being investigated in several ongoing trials in a variety of tumor types. Beyond Nexavar, Onyx has established a development pipeline of anticancer compounds at various stages of clinical testing, including carfilzomib, a next-generation proteasome inhibitor, that is currently being evaluated in multiple clinical trials for the treatment of patients with relapsed or relapsed/refractory multiple myeloma and solid tumors. ONX 0801, a targeted alpha-folate inhibitor, and ONX 0912, an oral proteasome inhibitor, are currently in Phase 1 testing. For more information about Onyx, visit the company's website at www.onyx-pharm.com.

Nexavar® (sorafenib) tablets is a registered trademark of Bayer HealthCare Pharmaceuticals.

(i) National Cancer Institute, Surveillance Epidemiology and End Results, 2007 Facts and Figures

(ii) International Agency for Research on Cancer, GLOBOCAN 2002 database

Forward-Looking Statements

This news release contains "forward-looking statements" of Onyx within the meaning of the federal securities laws.  These forward-looking statements include without limitation, statements regarding the progress and results of the clinical development, safety, regulatory processes, commercialization efforts or commercial potential of carfilzomib.  These statements are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including risks related to the development and commercialization of pharmaceutical products.  Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements.  Reference should be made to Onyx's Annual Report on Form 10-K for the year ended December 31, 2009, filed with the Securities and Exchange Commission under the heading "Risk Factors" and Onyx's Quarterly Reports on Form 10-Q for a more detailed description of such factors.  Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date of this release.  Onyx undertakes no obligation to update publicly any forward-looking statements to reflect new information, events, or circumstances after the date of this release except as required by law.  

SOURCE Onyx Pharmaceuticals, Inc.