Carfilzomib Data Demonstrate Promising Efficacy and Tolerability Signals in Ongoing Phase 1b/2 Combination Study with Lenalidomide and Low Dose Dexamethasone in Relapsed and/or Refractory Multiple Myeloma
Phase 3 Combination Trial Planned for 2010
New Orleans, LA. - Dec. 07, 2009
Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced interim results from the Phase 1b/2 006 study, demonstrating that carfilzomib, when administered with the standard therapies lenalidomide (Revlimid®) and low dose dexamethasone, is active and well-tolerated in patients with relapsed and/or refractory multiple myeloma. These data were presented at the 51st annual meeting of the American Society of Hematology (ASH) in New Orleans. A large, randomized international Phase 3 clinical trial studying the combination of lenalidomide and low dose dexamethasone with or without carfilzomib is planned for 2010.
"In many cases, responses were rapid and continued to improve with prolonged treatment, suggesting the combination may be appropriate for early disease control followed by chronic management of relapsed myeloma," said lead investigator Ruben Niesvizky, M.D., director of the Multiple Myeloma Service at the Center of Excellence for Lymphoma and Myeloma at New York Presbyterian Hospital-Cornell Medical Center. "Preliminary results from this study show no overlapping toxicities between carfilzomib and the lenalidomide and low dose dexamethasone combination. As a result, we were able to safely administer carfilzomib and lenalidomide at full doses for longer than ten months in some cases, despite the relapsed and often refractory status of disease in our patients. We look forward to further study of this important carfilzomib-based combination regimen."
The Phase 1b portion of the multicenter dose-escalation study enrolled 32 patients with relapsed and/or refractory multiple myeloma and is designed to evaluate safety and maximum tolerated or maximum per-protocol doses of carfilzomib with lenalidomide and low-dose dexamethasone. Dr. Niesvizky presented initial data on 27 patients evaluable for safety and 29 patients evaluable for efficacy. An additional 30 patients are being enrolled at the maximum per-protocol doses of these agents in the Phase 2 portion of this study; initial results are anticipated in that group in 2010.
The phase 1b population received one to three prior regimens for treatment of myeloma with 72 percent of the patients having received prior bortezomib, 87 percent prior immunomodulatory drug (IMiD) therapy (62 percent prior lenalidomide and 44 percent prior thalidomide), and 97 percent prior steroids. Forty-seven percent of the patients had disease refractory to the most recent therapy. The carfilzomib, lenalidomide and low-dose dexamethasone combination generated a response rate of 72 percent (minor response or better) and 59 percent (partial response or better), even though it included patients treated with less than maximal doses of carfilzomib and lenalidomide.
No dose-limiting toxicities were observed and the maximum tolerated dose has not been reached. The maximum per-protocol doses of 27mg/m2 carfilzomib and 25mg lenalidomide were safely administered. This maximum dosage will be administered in the Phase 2b portion of the trial and the planned Phase 3 trial.
Grade 3/4 adverse events were manageable and expected including neutropenia (6 patients), anemia (4 patients), hyperglycemia (3 patients), and thrombocytopenia (6 patients). The regimen was well tolerated with prolonged administration of more than 16 months, allowing for extended disease control. Initial responses typically occurred within 1 to 2 cycles, with many patients showing greater improvement over the subsequent months while remaining on initial doses of each agent.
"We believe carfilzomib's unique profile may position it to be a promising therapy to use in combination with one of the standard of care treatment regimens for relapsed myeloma - the combination of lenalidomide and low dose dexamethasone," said Michael Kauffman, M.D., Ph.D., interim chief medical officer at Onyx. "We look forward to initiating a Phase 3 trial in 2010 to evaluate carfilzomib in combination with lenalidomide and low dose dexamethasone, versus lenalidomide and dexamethasone alone, in patients with relapsed multiple myeloma."
Investor Teleconference
Principal investigators will discuss data presentations surrounding carfilzomib in relapsed or refractory multiple myeloma, as featured at ASH. The webcast event will begin at 9:00 a.m. CT/10:00 a.m. ET on December 7, 2009. The live webcast will be available at:
http://www.onyx-pharm.com/view.cfm/32/Event-Calendar
or by dialing 847-413-3362 and using the passcode 25914947. A replay of the presentation will be available on the Onyx website or by dialing 630-652-3044 and using the passcode 25914947 later in the day. The replay will be available on the Onyx website through January 7, 2010.
About Carfilzomib
Carfilzomib is a selective, next generation proteasome inhibitor that has shown encouraging results in a broad clinical trial program in multiple myeloma. Carfilzomib is currently undergoing evaluation as a single agent in multiple Phase 2 and Phase 1 clinical trials in relapsed or refractory multiple myeloma. These trials include a Phase 2b monotherapy study in patients with relapsed, refractory multiple myeloma, the pivotal trial that could support a new drug application (NDA) filing by the end of 2010. Carfilzomib is also being evaluated in advanced solid tumors.
About Multiple Myeloma
Multiple myeloma (MM) 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 MM and approximately 20,000 new cases are diagnosed annuallyi. Worldwide, more than 180,000 people are living with MM and approximately 86,000 new cases are diagnosed annuallyii.
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, is 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 anticipated benefits of the acquisition of Proteolix and the timing, 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 the risk that Proteolix's operations will not be integrated successfully into Onyx's, the risk that Onyx may not realize the anticipated benefits of the acquisition and 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, 2008, 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.
iNational Cancer Institute, Surveillance Epidemiology and End Results, 2007 Facts and Figures
iiInternational Agency for Research on Cancer , GLOBOCAN 2002 database