Onyx Pharmaceuticals Provides Update on Carfilzomib at 53rd American Society of Hematology Annual Meeting

SOUTH SAN FRANCISCO, Calif., Dec. 10, 2011 /PRNewswire/ -- Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced summaries of three poster presentations of single-agent carfilzomib, a next generation proteasome inhibitor, in patients with relapsed and/or refractory multiple myeloma at the 53rd American Society of Hematology (ASH) Annual Meeting in San Diego, CA. 

"This expanded data set supports our belief in the potential of carfilzomib to treat late-stage patients with relapsed and refractory multiple myeloma," said Ted W. Love, M.D., Executive Vice President and Head of Research and Development and Technical Operations at Onyx Pharmaceuticals.

Abstract #1877: Multivariate Modeling Reveals Evidence of a Dose-Response Relationship in Phase 2 Studies of Single-Agent Carfilzomib
In an analysis of 430 patients from Phase 2 studies, a highly significant dose-response relationship for carfilzomib was observed across key efficacy endpoints including the primary endpoint of overall response rate (ORR), as well as duration of response (DOR), time to progression (TTP), progression-free survival (PFS) and overall survival (OS). These observations were confirmed and quantified using a statistically rigorous, multivariate analysis. The dose response relationship was also apparent in the magnitude of response (partial response or better) across study participants. While a corresponding dose-toxicity analysis is ongoing, carfilzomib has been shown to have a similar tolerability profile at 20mg/m(2) and 27mg/m(2) doses. These findings are being further assessed in clinical trials evaluating higher dosing regimens.

Abstract #1876: Integrated Safety Data from Phase 2 Studies of Monotherapy Carfilzomib in Patients with Relapsed and Refractory Multiple Myeloma: An Updated Analysis
In an analysis of 526 patients, the authors concluded that these data confirm and extend earlier results indicating that single-agent carfilzomib has an acceptable safety profile in heavily pretreated patients with relapsed and refractory multiple myeloma. Carfilzomib was associated with a low rate of typically mild to moderate, non dose-limiting peripheral neuropathy (PN). PN of any grade was reported in 73 patients (14 percent) across the studies, and one patient (<1 percent) discontinued treatment due to a PN-related adverse event. In regard to renal events, less than 1 percent of patients discontinued treatment due to a renal event and 87 percent of patients had no worsening of renal function. Investigator-assessed cardiac events, some of which resulted in death possibly related to carfilzomib (<1 percent) or treatment discontinuation, were reported in this heavily pretreated, late-stage population. Cardiac failure events were reported in 7 percent of patients regardless of causality. Cardiac events resulting in treatment discontinuation included congestive heart failure (2 percent), cardiac arrest (1 percent) and myocardial ischemia (<1 percent). The extent to which cardiac events were due to patients' baseline comorbidities, toxicity from prior treatments, effects of multiple myeloma, carfilzomib itself, or a combination of these factors could not be determined. Rates and causes of death were consistent with those observed in heavily pretreated patients with end-stage multiple myeloma.

Abstract #1875: Unfavorable Cytogenetic Characteristics do not Adversely Impact Response Rates in Patients with Relapsed and/or Refractory Multiple Myeloma Treated with Single-Agent Carfilzomib on the 003-A1 Study
This analysis evaluated the impact of specific cytogenetic abnormalities on efficacy and treatment outcomes including response rates, time-to-event endpoints, and OS. In patients with multiple myeloma, cytogenetic abnormalities with certain genetic variations have a well-documented but variable adverse impact on therapeutic response and time to event. Of the 229 evaluable patients, 71 patients had unfavorable cytogenetic status. Cytogenetic abnormalities are defined as the presence of del 13 or hypodiploidy by metaphase cytogenetic analysis and/or del 17p13, t(4;14), t (14;16) by fluorescence in situ hybridization (FISH).  An analysis of the results showed that response rates to carfilzomib among patients with normal/favorable cytogenetics were comparable to rates among patients with unfavorable cytogenetic abnormalities.

About the Phase 2 studies

• The 003-A0 study was an open-label, single-arm, Phase 2 study of carfilzomib in patients with relapsed and refractory multiple myeloma. The primary endpoint was ORR, and secondary endpoints included CBR, DOR, PFS, TTP and safety. Patients in the 003-A0 trial received carfilzomib at a dose of 20mg/m(2).
• 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 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]  Patients received carfilzomib at a dose of 20mg/m(2⁾ for the first cycle, and were then dose-escalated to 27mg/m(2). The primary endpoint was ORR. Secondary endpoints included DOR, CBR, OS, TTP, PFS, and safety. 
• The 004 study, an open-label, single-agent Phase 2 study of carfilzomib, was conducted in collaboration with the Multiple Myeloma Research Consortium (MMRC) and other institutions, and enrolled 129 patients with relapsed and/or refractory multiple myeloma who had received one to three prior treatments. Patients were divided into two populations: bortezomib-naive patients and patients previously treated with bortezomib. Prior therapies included alkylating agents, stem cell transplant, thalidomide, lenalidomide and anthracyclines, and bortezomib in the bortezomib-treated patients. The primary endpoint was ORR and secondary endpoints included CBR, TTP, DOR, OS and safety.
• The 005 study was an open-label, single-agent Phase 2 study evaluating the safety and pharmacokinetics of carfilzomib in 50 patients with relapsed and refractory multiple myeloma with renal dysfunction. The primary endpoint was pharmacokinetics; the secondary endpoint was safety.

ASH Investor Teleconference
Investigators and members of the Onyx management team will highlight data presented on carfilzomib featured at the 53rd ASH Annual Meeting and Exposition in San Diego, CA. The teleconference will begin at 10:00 a.m. PT on December 13, 2011.

Interested parties may access the teleconference and the presentation that accompanies it on our website at:  
http://www.onyx-pharm.com/investors/event-calendar

or by dialing 847-585-4405 and using the passcode 31296220.  A replay of the presentation will be available on the Onyx website or by dialing 630-652-3042 and using the passcode 31296220# later in the day.  The replay will be available on the Onyx website until December 27, 2011.

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

• A Phase 3 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 3 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.
• An expanded access program is underway in partnership with the Multiple Myeloma Research Foundation for eligible patients in the U.S., with relapsed and refractory multiple myeloma for whom no satisfactory treatment alternatives are available.

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-pharm.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] Anderson et al. Clinically relevant end points and new drug approvals for myeloma. Leukemia. 2008. 22:231

[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.