Onyx Pharmaceuticals Presents Carfilzomib Data at 53rd American Society of Hematology Annual Meeting

SOUTH SAN FRANCISCO, Calif., Dec. 12, 2011 /PRNewswire/ -- Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced final results from a Phase 2 study, known as the 004 study, evaluating single-agent carfilzomib, a next generation proteasome inhibitor, in patients with relapsed and/or refractory multiple myeloma. Results on prolonged infusion of carfilzomib and speed of response were also announced. These data were presented at the 53rd American Society of Hematology (ASH) Annual Meeting in San Diego, CA.

Abstract #813: Final Results from the Bortezomib-Naive Group of PX-171-004, a Phase 2 Study of Single-Agent Carfilzomib in Patients with Relapsed and/or Refractory Multiple Myeloma
Results from the 004 Phase 2 study evaluated single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who had received one to three prior treatments and had not been previously treated with bortezomib. In 67 evaluable patients, carfilzomib achieved an overall response rate (ORR) of 52 percent and a clinical benefit rate (CBR) of 64 percent when administered at 27mg/m(2). Sixty-four percent of patients were refractory to their most recent therapy prior to entering the trial. Overall response is defined as a partial response or greater.[i]  The median time-to-progression (TTP), duration of response (DOR) and overall survival (OS) were not reached in this study, designed to provide patients with up to 12 cycles of carfilzomib.  Forty-two percent of patients completed greater than 10 cycles and 22 patients continued treatment beyond one year in the extension protocol PX-171-010.

"This Phase 2 study demonstrates promising single-agent activity of carfilzomib in patients with relapsed and/or refractory multiple myeloma who have not been previously treated with bortezomib," said Ravi Vij, M.D., Associate Professor, Department of Medicine, Oncology Division, Bone Marrow Transplantation & Leukemia Section at the Washington University School of Medicine, who presented the data. "The efficacy and safety results from this study suggest that carfilzomib has the potential to be used in earlier lines of treatment in patients with multiple myeloma."

Patients were divided into two cohorts. In Cohort 1 (n=59), patients received 20mg/m(2) for all treatment cycles.  In Cohort 2 (n=67), patients received a dose-escalating regimen of 20mg/m(2) for the first cycle and 27mg/m(2) for all remaining treatment cycles.

The 59 evaluable patients who received carfilzomib at 20mg/m(2) achieved an ORR of 42 percent and a CBR of 59 percent. This cohort demonstrated a TTP of 8.3 months and a DOR of 13.1 months. The median overall survival (OS) has not yet been reached.  Sixty-six percent of these patients were refractory to their most recent therapy prior to entering the trial.

No new or unexpected adverse events were observed. The most common Grade 3 treatment-emergent adverse events included: anemia (Cohort 1, 12 percent; Cohort 2, 17 percent); thrombocytopenia (Cohort 1, 15 percent; Cohort 2, 11 percent); neutropenia (Cohort 1, 12 percent; Cohort 2, 14 percent); lymphopenia (Cohort 1, 14 percent; Cohort 2, 19 percent); and pneumonia (Cohort 1, 14 percent; Cohort2, 11 percent). Peripheral neuropathy of any grade was infrequent.

"This trial highlights our commitment to understanding carfilzomib across treatment settings," said Ted W. Love, M.D., Executive Vice President and Head of Research and Development and Technical Operations at Onyx Pharmaceuticals. "Efficacy and safety data from this trial was included as part of the New Drug Application (NDA) for carfilzomib that was recently accepted by the U.S. Food and Drug Administration (FDA) under the accelerated approval process for the treatment of patients with relapsed and refractory multiple myeloma."

Abstract #2930: A Phase 1b/2 Study of Prolonged Infusion Carfilzomib in Patients with Relapsed and/or Refractory Multiple Myeloma: Updated Efficacy and Tolerability from the Completed 20/56 mg/m(2) Expansion Cohort of PX-171-007
The Phase 1b/2 study evaluated the safety and efficacy of a prolonged, 30-minute infusion of carfilzomib at a dose of 56mg/m(2) in 24 patients who previously had received a median of 4.5 lines of therapy. Authors observed a 60 percent ORR and an acceptable safety profile at this dose in these heavily pretreated patients.  These results support preclinical findings that longer infusion times enable higher doses and achieve greater levels of proteasome inhibition.

Abstract #3969: The Speed of Response to Single-Agent Carfilzomib in Patients with Relapsed and/or Refractory Multiple Myeloma: An Exploratory Analysis of Results from Two Multicenter Phase 2 Clinical Trials
An analysis of two Phase 2 studies demonstrated that the speed of response to carfilzomib was rapid. Rapid response was defined as achievement of minimal response or better within a median of 0.5 to 1.0 months. When results were analyzed according to baseline characteristics, there was a trend of longer times to clinical benefit response in patients with a greater number of prior therapeutic regimens.

About the Phase 2 Studies

• 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 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.[ii]  The primary endpoint was ORR. Secondary endpoints included DOR, CBR, OS, TTP, PFS, and safety. 
• The 007 study is an open-label Phase 1b/2 study. Results were reported from the dose-expansion phase of this ongoing study, which evaluated the safety and efficacy of a prolonged, 30-minute infusion of carfilzomib at a dose of 56mg/m(2). Endpoints included ORR, DOR, PFS, TTP, pharmacokinetics and 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 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.
• A Phase 1b/2 study, known as the 006 study, is evaluating carfilzomib in combination with lenalidomide and low dose dexamethasone in patients with relapsed and/or refractory myeloma.
• A MMRC Phase 1/2 study is evaluating carfilzomib in combination with lenalidomide and low dose dexamethasone in newly diagnosed patients. This study is supported by Onyx Pharmaceuticals, MMRC, and Celgene Corporation.  
• 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.
• 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.[iii] Worldwide, more than 180,000 people are living with multiple myeloma and approximately 86,000 new cases are diagnosed annually.[iv]

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]Partial response is defined by greater than or equal to 50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by greater than or equal to 90% or to less than 200 mg per 24 hours, International Uniform Response Criteria for Multiple Myeloma
Published in Leukemia (2006) 20:1467-1473) with an Erratum in Leukemia (2007)21:1134-1135

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

[iii] National Cancer Institute, Surveillance Epidemiology and End Results, 2007 Facts and Figures

[iv] iInternational Agency for Research on Cancer, GLOBOCAN 2002 database

SOURCE Onyx Pharmaceuticals, Inc.