Onyx Pharmaceuticals Announces Updated Pivotal Carfilzomib Phase 2B Data

SOUTH SAN FRANCISCO, Calif., May 19, 2011 /PRNewswire/ -- Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced updated results from the Phase 2b 003-A1 study of single-agent carfilzomib, a next generation proteasome inhibitor, in patients with relapsed and refractory multiple myeloma. Carfilzomib achieved a clinical benefit rate (CBR) (minimal response or greater) in the study population of 37 percent with a duration of response (DOR) of 8.3 months.  The primary endpoint, overall response rate (ORR) (defined as partial response or greater) was 24 percent with a median duration of response (DOR) of 7.8 months.  Patients entered the study after receiving a median of five prior lines of therapy (corresponding to a median of 13 anti-myeloma agents). The median overall survival (OS) for all patients in the study, regardless of response to drug, was 15.6 months. Overall survival for the best responding patients (partial response or greater) is continuing to mature (subject to additional patient observations) and is currently 20.7 months.  These data are being presented at the upcoming 47th American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago by David Siegel, M.D., Ph.D., Division Chief for Myeloma at John Theurer Cancer Center at Hackensack University Medical Center, June 3 – 7, 2011.

Based on the full 003-A1 results, Onyx intends to submit a New Drug Application (NDA) filing for accelerated approval in the July/August timeframe.

"As expected, studies mature and results are updated with minor variability in data observed," said Ted Love, M.D., Executive Vice President, R&D and Technical Operations.  "We are particularly pleased to see the overall survival trend improving for the best responding patients.  Onyx looks forward to filing an NDA in the July to August timeframe based on the positive findings in the 003-A1 study of carfilzomib in relapsed and refractory multiple myeloma."

The most common Grade 3/4 adverse events were thrombocytopenia (29 percent), anemia (24 percent), lymphopenia (20 percent), and neutropenia (11 percent).  

Two hundred and sixty-six patients with relapsed and refractory multiple myeloma were enrolled in the study, and 257 patients were evaluable for response. The primary endpoint was ORR. Secondary endpoints included CBR, DOR, OS, and safety.

About the Carfilzomib Development Program

The carfilzomib development program includes a large, randomized international Phase 3 clinical trial, known as the ASPIRE trial, studying the combination of lenalidomide and low dose dexamethasone with or without carfilzomib in patients with relapsed multiple myeloma. The company received Scientific Advice from the European Medicines Agency (EMA) and has an agreement with the U.S. Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) on the design and planned analysis of the ASPIRE trial. Carfilzomib is also being evaluated in the Phase 3 European FOCUS trial, which is designed to support a European registrational filing.  The FOCUS trial protocol is currently being modified to determine a potential mortality benefit for carfilzomib.  Carfilzomib is also being evaluated in a broad investigator sponsored trial program including 1st line multiple myeloma, combination studies, lymphoma and other malignancies.

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.(i) 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 selective 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, an alpha-folate receptor targeted inhibitor of thymidylate synthase, 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.

Important Safety Considerations for Patients Taking Nexavar

Nexavar in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer.

Nexavar may cause fetal harm when administered to a pregnant woman. Women of childbearing potential are advised to avoid becoming pregnant and female patients should also be advised against breastfeeding while receiving Nexavar.

Cardiac ischemia and/or myocardial infarction may occur. Temporary or permanent discontinuation of Nexavar should be considered in patients who develop cardiac ischemia and/or myocardial infarction.

Gastrointestinal perforation was an uncommon adverse reaction and has been reported in less than 1% of patients taking Nexavar.

Uncommon but serious adverse reactions, including keratoacanthomas/squamous cell cancer of the skin and Stevens-Johnson Syndrome, have been reported in clinical trials.

An increased risk of bleeding may occur following Nexavar administration. If bleeding necessitates medical intervention, consider discontinuation of Nexavar.

Hypertension may occur early in the course of treatment. Monitor blood pressure weekly during the first 6 weeks and periodically thereafter and treat, as required.

Hand-foot skin reaction and rash are common and management may include topical therapies for symptomatic relief. In cases of any severe or persistent adverse reactions, temporary treatment interruption, dose modification, or permanent discontinuation of Nexavar should be considered. Temporary interruption of Nexavar therapy is recommended in patients undergoing major surgical procedures.

Elevations in serum lipase and reductions in serum phosphate of unknown etiology have been associated with Nexavar. Caution is recommended when administering Nexavar with compounds that are metabolized/eliminated predominantly by the UGT1A9 pathway, UGT1A1 pathway (eg, irinotecan), doxorubicin, docetaxel, fluorouracil, and substrates of CYP2B6 and CYP2C8, and CYP3A4 inducers. Concomitant use of carboplatin and paclitaxel with sorafenib resulted in an increase in paclitaxel exposure and an increase in Nexavar exposure. Patients taking concomitant warfarin should be monitored regularly for changes in prothrombin time, INR, or clinical bleeding episodes. Nexavar exposure decreases when coadministered with oral neomycin. Effects of other antibiotics on Nexavar pharmacokinetics have not been studied.

Most common adverse reactions reported for Nexavar-treated patients vs placebo-treated patients in unresectable HCC, respectively, were: diarrhea (55% vs 25%), fatigue (46% vs 45%), abdominal pain (31% vs 26%), weight loss (30% vs 10%), anorexia (29% vs 18%), nausea (24% vs 20%), and hand-foot skin reaction (21% vs 3%). Grade 3/4 adverse reactions were 45% vs 32%.

Most common adverse reactions reported for Nexavar-treated patients vs placebo-treated patients in advanced RCC, respectively, were: diarrhea (43% vs 13%), rash/desquamation (40% vs 16%), fatigue (37% vs 28%), hand-foot skin reaction (30% vs 7%), alopecia (27% vs 3%), and nausea (23% vs 19%). Grade 3/4 adverse reactions were 38% vs 28%.

During postapproval use of Nexavar, the following adverse drug reactions have been identified: angioedema and drug-induced hepatitis, including reports of hepatic failure and death.

For information about Nexavar including U.S. Nexavar prescribing information, visit www.nexavar.com or call 1.866.NEXAVAR (1.866.639.2827).

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

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

SOURCE Onyx Pharmaceuticals, Inc.