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Onyx Pharmaceuticals' Carfilzomib Continues to Demonstrate Encouraging Results in Ongoing Phase 2 Multiple Myeloma Study

Sunday, June 6, 2010 General News J E 4
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Fifty-five Percent Single-Agent Response Rate in Relapsed/Refractory Setting

EMERYVILLE, Calif., June 5 /PRNewswire-FirstCall/ -- Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced interim results from an ongoing Phase 2 study, known as the 004 study.  Carfilzomib, a selective, next-generation proteasome inhibitor, demonstrated encouraging overall response rates (ORR), tolerability and durable disease control when administered as a single-agent in patients with relapsed and/or refractory multiple myeloma.  In 53 evaluable patients who had not been previously treated with bortezomib (Velcade®), carfilzomib achieved an overall response rate of 55 percent at 27mg/m2. Patients in this group also achieved time-to-progression (TTP) of 11.5 months and duration of response (DOR) of 11.5 months.  Forty 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)

These data are being presented today at the 46th American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago by Ravi Vij, M.D., Associate Professor, Department of Medicine, Oncology Division, Bone Marrow Transplantation & Leukemia Section at the Washington University School of Medicine.

"Although there are no direct comparative studies, based on historical controls, carfilzomib is exhibiting one of the highest single agent response rates and longest durations of response in patients with multiple myeloma who have had one to three prior therapies in this ongoing Phase 2 study," said Dr. Vij. "The data from this trial support carfilzomib's potential to benefit patients with multiple myeloma who are no longer responding to current therapies."

One hundred fifty-five patients with relapsed and/or refractory multiple myeloma were enrolled in the study and were divided into two populations: patients who had not received prior bortezomib treatment (bortezomib-naive) and those who had received prior bortezomib treatment (bortezomib-treated).  Of the 119 bortezomib-naive patients, 53 evaluable patients received carfilzomib at 27mg/m2 and 53 evaluable patients received carfilzomib at 20mg/m2. On the bortezomib-treated arm, 34 evaluable patients received carfilzomib at 20mg/m2 and were not dose escalated.

The 53 evaluable bortezomib-naive patients who received carfilzomib at 20mg/m2 achieved an ORR of 45 percent.  Other interim results at the 20mg/m2 included TTP of 8.3 months and DOR of 10.2 months.  Forty-nine percent of these patients were refractory to their most recent therapy prior to entering the trial.

The 34 evaluable patients previously treated with bortezomib achieved an ORR of 21 percent when treated with carfilzomib at the 20mg/m2 dose. Secondary endpoints included TTP of 8.1 months and DOR of 11.5 months.  Forty-two percent of these patients were refractory to their most recent therapy prior to entering the trial.

In the overall study population, treatment with carfilzomib was well-tolerated, and no new or unexpected adverse events occurred. The most common Grade 3 treatment-emergent adverse events included: pneumonia (11 percent), anemia (9.7 percent), neutropenia (9.7 percent) and thrombocytopenia (9 percent). Peripheral neuropathy of any grade was infrequent and no Grade 4 adverse events were observed.

"This data from the 004 study will be included in the planned U.S. New Drug Application (NDA) that we intend to file by year-end 2010, pending top-line data from the ongoing registration trial, known as the 003-A1 study.  The results from 003-A1, a Phase 2b trial, will form the basis for the NDA, which we expect to file under the accelerated approval mechanism," stated Michael Kauffman, M.D., Ph.D., Chief Medical Officer at Onyx. "In addition, we have announced our intention to initiate an international Phase 3 clinical trial evaluating carfilzomib in combination with lenalidomide and low dose dexamethasone in earlier stage myeloma.  This trial is being conducted through a Special Protocol Assessment with the U.S. Food and Drug Administration and with Scientific Advice from the European Medicines Agency."

Phase 2 004 Trial Design

The open-label, single agent ongoing Phase 2 study, known as the 004 study, is being conducted in collaboration with the Multiple Myeloma Research Consortium, and enrolled approximately 150 patients with relapsed and/or refractory multiple myeloma who have received 1-3 prior treatments. Patients include two populations: bortezomib-naive patients with relapsed and/or refractory multiple myeloma and bortezomib-treated patients with relapsed and/or refractory multiple myeloma. Prior therapies include alkylating agents, stem cell transplant, thalidomide, lenalidomide and anthracyclines, and bortezomib in the bortezomib-treated patients.  The primary endpoint is ORR and secondary endpoints include TTP, DOR, overall survival and safety.

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 monotherapy 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 clinical trial evaluating the combination of lenalidomide and low dose dexamethasone with or without carfilzomib in patients with relapsed multiple myeloma is expected to begin shortly. 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 009 trial. Carfilzomib is also being evaluated in advanced solid tumors.

A second Phase 3 European clinical trial of carfilzomib is planned in relapsed/refractory myeloma and is designed to support a registrational filing with the EMA. 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.(ii) 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 MM and approximately 86,000 new cases are diagnosed annually.(iii)

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.

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.  

(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 < 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) 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.

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