2012 Press Releases
Onyx Pharmaceuticals Announces KyprolisTM Study Published in the Medical Journal Blood
First Peer-Reviewed Publication of Full Data Results from 003-A1 Study
South San Francisco, CA. Jul. 25, 2012
Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) announced today that Blood, the medical journal of the American Society of Hematology, has published results from the 003-A1 Phase 2b trial, a single-arm, multicenter clinical trial evaluating Kyprolis™ (carfilzomib) for Injection for the treatment of patients with advanced multiple myeloma, who had received a median of five prior anti-myeloma regimens. The lead author was Dr. David Siegel, Chief of the Division of Multiple Myeloma at John Theurer Cancer Center at Hackensack University Medical Center.
On July 20, 2012, the U.S. Food and Drug Administration (FDA) granted accelerated approval of Kyprolis for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent (IMiD), and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval was based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified. Full prescribing information is available at http://www.onyx.com.
About the 003-A1 Study
Two hundred and sixty-six patients with relapsed multiple myeloma who had received at least two prior therapies including bortezomib and an IMiD were enrolled in the open-label, single-arm 003-A1 Phase 2b study, and 257 patients were evaluable for response. The authors reported on the primary endpoint and secondary endpoints of the 003-A1 trial. The primary endpoint was overall response rate (ORR), defined as partial response (PR) or greater. The ORR was 23.7% among response-evaluable patients (n=257), and 22.9% among the total patient population (n=266). The median duration of response was 7.8 months. The most common treatment-emergent adverse events (AEs) reported in this study were fatigue (49%) and anemia (46%), and the most common Grade 3/4 AEs were thrombocytopenia (29%) and anemia (24%). The most common AEs of any grade possibly related to carfilzomib were fatigue (37%) and nausea (34%).
Data from the 003-A1 study were previously presented at the 52nd American Society of Hematology Annual Meeting in December 2010 and at subsequent international scientific meetings. The trial was conducted in collaboration with the Multiple Myeloma Research Consortium (MMRC) and at additional sites in the United States and Canada.
Important Safety Information Regarding Kyprolis™ (carfilzomib) for Injection
Safety data have been evaluated in 526 patients with relapsed and/or refractory multiple myeloma who received single-agent carfilzomib. There were 37 deaths in the phase 2 studies, or 7% of patients. The most common causes of death, other than disease progression, were cardiac (5 patients), end-organ failure (4 patients), and infection (4 patients). Important warnings and precautions include cardiac arrest, congestive heart failure, myocardial ischemia; pulmonary hypertension, pulmonary complications, infusion reactions, tumor lysis syndrome, thrombocytopenia, hepatic toxicity and embryo-fetal toxicity.
Death due to cardiac arrest has occurred within a day of Kyprolis administration. Patients with New York Heart Association Class III and IV heart failure, myocardial infarction in the preceding 6 months, and conduction abnormalities uncontrolled by medications were not eligible for the clinical trials. These patients may be at greater risk for cardiac complications.
Pulmonary arterial hypertension (PAH) was reported in 2% of patients treated with Kyprolis and was Grade 3 or greater in less than 1% of patients. Dyspnea was reported in 35% of patients enrolled in clinical trials. Grade 3 dyspnea occurred in 5%; no Grade 4 events, and 1 death (Grade 5) was reported.
Infusion reactions, characterized by a spectrum of systemic symptoms including fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina can occur immediately following or up to 24 hours after administration of Kyprolis. Administration of dexamethasone prior to Kyprolis reduces the incidence and severity of reactions. Tumor lysis syndrome (TLS) occurred following Kyprolis administration in < 1% of patients. Patients with multiple myeloma and a high tumor burden should be considered to be at greater risk for TLS.
Thrombocytopenia following Kyprolis administration resulted in a dose reduction in 1% of patients and discontinuation of treatment with Kyprolis in < 1% of patients.
Cases of hepatic failure, including fatal cases, have been reported (< 1%). Kyprolis can cause elevations of serum transaminases and bilirubin.
There are no adequate and well-controlled studies in pregnant women using Kyprolis. Females of reproductive potential should be advised to avoid becoming pregnant while being treated with Kyprolis.
The most common serious adverse reactions were pneumonia, acute renal failure, pyrexia, and congestive heart failure. The most common adverse reactions (incidence of 30% or greater) observed in clinical trials of patients with multiple myeloma were fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and pyrexia. Serious adverse reactions were reported in 45% of patients.
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 220,000 people are living with multiple myeloma and approximately 100,000 new cases are diagnosed annually.ii
About the Kyprolis™ (carfilzomib) for Injection Development Program
Kyprolis is being studied in several clinical trials either as a single-agent or in combination with other therapies, including:
- A global Phase 3 clinical trial, known as the ASPIRE trial, has completed enrollment and is evaluating the combination of lenalidomide and low-dose dexamethasone with or without Kyprolis 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) and has received Scientific Advice from the European Medicines Agency (EMA) on the design and planned analysis of the trial.
- A Phase 3 clinical trial, known as the FOCUS trial, is evaluating single-agent Kyprolis in patients with relapsed and refractory myeloma who have received three or more prior therapies. The trial is designed to facilitate regulatory approvals around the world.
- A global head-to-head Phase 3 clinical trial, known as the ENDEAVOR trial, is evaluating the combination of Kyprolis and low-dose dexamethasone versus the combination of bortezomib and low-dose dexamethasone.
- A Phase 1/2 study being conducted by Onyx’s partner Ono Pharmaceutical Co., Ltd. is evaluating Kyprolis in Japanese patients with relapsed/refractory multiple myeloma.
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. 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.com.
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 capabilities or efforts or commercial potential of Kyprolis (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, 2011, 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 American Cancer Society, Cancer Facts & Figures 2012
ii International Agency for Research on Cancer, GLOBOCAN 2010