SOUTH SAN FRANCISCO, CA -- (Marketwire) -- 02/20/13 -- Onyx Pharmaceuticals, Inc. (NASDAQ: ONXX) announced today that Leukemia has published results from the Phase 2 trial known as PX-171-005 (NCT00721734), an open-label, multicenter clinical trial evaluating Kyprolis® (carfilzomib) for Injection in patients with relapsed and refractory multiple myeloma and varying degrees of renal insufficiency. The article is titled, "Carfilzomib in Multiple Myeloma Patients With Renal Impairment: Pharmacokinetics and Safety." The lead author was Dr. Ashraf Badros, Professor of Medicine at the University of Maryland Greenebaum Cancer Center.
"Renal impairment is a frequent and severe complication in patients with multiple myeloma, and presents challenges in the utilization of some anti-myeloma therapies," said Dr. Badros. "This prospective study provides important data for carfilzomib use across the spectrum of renal impairment, from patients presenting with minimal impairment to those on chronic hemodialysis."
About the PX-171-005 Study
Fifty patients with relapsed, refractory and/or progressive multiple myeloma who had received at least two prior therapeutic regimens were enrolled in the open-label, single-agent, multicenter Phase 2 trial, and 47 were evaluable for response. The authors reported on the primary and secondary endpoints of the trial. The primary endpoint was the influence of renal impairment on the pharmacokinetics (PK) of carfilzomib. Statistical comparisons showed no differences between renal function status and the dose-adjusted PK parameters including apparent plasma clearance, dose-normalized AUCinf (total exposure), and the dose-normalized Cmax. Secondary outcomes included safety, tolerability, pharmacodynamic (PDn) measures, and efficacy. The most common treatment-emergent adverse events (AEs) reported in this study were fatigue (56%) and anemia (50%), and the most common Grade 3/4 AEs were anemia (28%), thrombocytopenia (20%). The most common AEs of any grade possibly related to carfilzomib were fatigue (56%), anemia (50%), nausea (36%), and diarrhea (36%).
Data from the trial were initially presented at the 2010 American Society of Clinical Oncology Annual Meeting and at subsequent international scientific meetings. The trial was conducted at five sites in the United States. An electronic version of the article can be accessed at http://www.nature.com/leu/journal/vaop/naam/pdf/leu201329a.pdf.
Important Indication and Safety Information for Kyprolis® (carfilzomib) for Injection
On July 20, 2012, the U.S. Food and Drug Administration (FDA) granted accelerated approval of Kyprolis® (carfilzomib) for Injection 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.
Safety data were evaluated in 526 patients with relapsed and/or refractory multiple myeloma who received single-agent KYPROLIS. 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.
Full prescribing information is available at http://www.kyprolis.com.
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.(1) Worldwide, more than 220,000 people are living with multiple myeloma and approximately 100,000 new cases are diagnosed annually.(2)
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.
Kyprolis® is a registered trademark of Onyx Pharmaceuticals, Inc.
Note Regarding PX-171-005 Study
This news release includes partial results from the PX-171-005 study. The partial results contained herein should be considered within the context of the full PX-171-005 study results, which are discussed in greater detail in the article titled, "Carfilzomib in Multiple Myeloma Patients With Renal Impairment: Pharmacokinetics and Safety," which can be accessed by following the link in this news release.
(1) American Cancer Society, Cancer Facts & Figures 2012
(2) International Agency for Research on Cancer, GLOBOCAN 2010
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