Onyx Pharmaceuticals Completes Enrollment in ASPIRE Phase 3 Carfilzomib Combination Trial for the Potential Treatment of Relapsed Multiple Myeloma

SOUTH SAN FRANCISCO, Calif., Feb. 22, 2012 /PRNewswire/ -- Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced that it has reached the target 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) for a Special Protocol Assessment (SPA) and has received Scientific Advice from the European Medicines Agency (EMA) on the design and planned analysis of the ASPIRE trial.

"The ASPIRE trial, which is designed to support full approval of carfilzomib for patients with relapsed multiple myeloma, is an important component of our overall regulatory strategy to bring carfilzomib to the broadest number of patients in need of new treatment options," said Ted W. Love, M.D., Executive Vice President and Head of Research and Development and Technical Operations at Onyx Pharmaceuticals. "We are pleased to have completed enrollment in the ASPIRE study ahead of schedule, and could have interim results as early as the first half of 2013."

The FDA is currently reviewing a New Drug Application (NDA) for potential accelerated approval of carfilzomib in the U.S. for the treatment of patients with relapsed and refractory multiple myeloma. The Prescription Drug User Fee Act (PDUFA) date for completion of the NDA review by the FDA is July 27, 2012.

Phase 3 Trial Design
The ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma) trial is 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 were 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 targeted enrollment of 780 patients and is being conducted at approximately 200 sites in North America, Europe, and Israel. For information about this study, please visit www.clinicaltrials.gov.  

Phase 1/2 Study Results

As previously reported at the 47thAmerican 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 78 percent in 51 evaluable patients. The combination was well tolerated and demonstrated activity, including in patients who had received prior bortezomib treatment and an immunomodulatory drug (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 administered. The most common Grade 3/4 adverse events included neutropenia (23%), thrombocytopenia (15%), anemia (15%), hypophosphatemia (13%), fatigue (12%), hyperglycemia (8%), lymphopenia (8%), hyponatremia (6%), diarrhea (6%) and pneumonia (6%). Hematologic adverse events were reversible and manageable.

About the Carfilzomib Development Program

A new drug application (NDA) was submitted to the FDA based on the carfilzomib 003-A1 study, an open-label, single-arm Phase 2b 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.(i) 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 who participated in Phase 2 trials.  The NDA was accepted for standard review through the accelerated pathway, and the anticipated date for completion of review by the FDA is July 27, 2012.

In addition to ASPIRE, carfilzomib is currently being studied in several clinical trials either as a single-agent or in combination with other therapies, including:

• A Phase 3 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 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.

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 United States, more than 50,000 people are living with multiple myeloma and approximately 20,000 new cases are diagnosed annually.(ii) Worldwide, more than 180,000 people are living with multiple myeloma and approximately 86,000 new cases are diagnosed annually.(iii)

About Onyx Pharmaceuticals, Inc.

Based in South San Francisco, California, Onyx Pharmaceuticals, Inc. is a global biopharmaceutical company engaged in the development and commercialization of innovative therapies for improving the lives of people with cancer and other serious diseases.  The company is focused on developing novel medicines that target key molecular pathways. For more information about Onyx, visit the company's website at www.onyx.com.

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, the expanded access program, 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 submission, review, potential approval of the NDA, 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, 2010, 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.

(i) http://www.fda.gov/forconsumers/byaudience/forpatientadvocates/speedingaccesstoimportantnewtherapies/ucm128291.htm
(ii) National Cancer Institute, Surveillance Epidemiology and End Results, 2007 Facts and Figures
(iii) International Agency for Research on Cancer, GLOBOCAN 2002 database

SOURCE Onyx Pharmaceuticals, Inc.