The US Food and Drug Administration (FDA) has granted accelerated approval for Onyx Pharmaceuticals' Kyprolis (carfilzomib) for injection, a proteasome inhibitor, indicated for the treatment of patients with multiple myeloma who have received at least two prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of completion of the last therapy.
The indication for Kyprolis is based on response rate. Currently, no data are available for Kyprolis that demonstrate an improvement in progression-free survival or overall survival.
“Today’s approval is a significant milestone for Onyx and, most importantly, for patients with advanced myeloma who have few treatment options available to them,” said N Anthony Coles, MD, president and CEO of Onyx Pharmaceuticals. “We deeply appreciate the hundreds of patients who participated in the Kyprolis clinical studies that led to this accelerated approval, and recognize the many clinicians across the country and researchers here at Onyx for their dedication in bringing this promising new medicine to patients. We are committed to continuing the clinical development of Kyprolis across earlier stages of multiple myeloma treatment.”
The approval was based on the results of the phase II b 003-A1 study, a single-arm, multicentre clinical trial that enrolled 266 patients with multiple myeloma, who had received a median of five prior anti-myeloma regimens. The primary efficacy endpoint was overall response (ORR) and determined by an Independent Review Committee using the International Myeloma Working Group (IMWG) criteria. ORR was 22.9 per cent and median response duration was 7.8 months.
Safety data were evaluated in 526 patients with relapsed and/or refractory multiple myeloma who received single-agent carfilzomib. There were 37 deaths on study, or seven per cent of patients. The most common causes of death, other than disease progression, were cardiac (five patients), end-organ failure (four patients), and infection (four patients). Important warnings and precautions include cardiac arrest, congestive heart failure, myocardial ischemia; pulmonary hypertension, pulmonary complications, infusion reactions, infusion reactions, tumor lysis syndrome, thrombocytopenia, hepatic toxicity and embryo-fetal toxicity. The most common serious adverse reactions were pneumonia, acute renal failure, pyrexia, and congestive heart failure. The most common adverse reactions (incidence of 30 per cent or greater) observed in clinical trials of patients with multiple myeloma were fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhoea, and pyrexia. Serious adverse reactions were reported in 45 per cent of patients.
“This approval provides a new treatment option for the significant unmet need that exists in patients with multiple myeloma who have progressed after use of available treatments,” said Dr David Siegel, Chief of the Division of Multiple Myeloma at John Theurer Cancer Centre at Hackensack University Medical Center. “The single-agent activity of Kyprolis provides clinicians the opportunity to help these patients who until now had no effective options.”
Enrollment has been completed for the phase III confirmatory clinical trial, known as the ASPIRE trial. The company has an agreement with the FDA on a Special Protocol Assessment (SPA) for this trial.
Onyx also announced the availability of Onyx Pharmaceuticals 360 (Onyx 360), a comprehensive patient and caregiver support and services program, designed to help patients navigate the treatment journey, including reimbursement and payment support, treatment support and referrals to third-party organizations for day-to-day and emotional support.
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.