Amgen (AMGN) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending a label variation for KYPROLIS® (carfilzomib) to include the final overall survival (OS) data from the Phase 3 ASPIRE trial. The ASPIRE trial demonstrated that the addition of KYPROLIS to lenalidomide and dexamethasone (KRd) reduced the risk of death by 21 percent versus lenalidomide and dexamethasone alone (Rd) and extended OS by 7.9 months in patients with relapsed or refractory multiple myeloma (median OS 48.3 months for KRd versus 40.4 months for Rd, HR = 0.79, 95 percent CI, 0.67 – 0.95; 1-sided p=0.0045).
“This latest positive CHMP opinion marks the second time Amgen will add overall survival data from a Phase 3 study to the label, further validating the fundamental role of KYPROLIS in treating patients with relapsed or refractory multiple myeloma,” said David M. Reese, M.D., senior vice president of Translational Sciences and Oncology at Amgen. “This is a major step towards advancing KYPROLIS-based regimens as standard of care, and we look forward to the European Commission’s decision later this year.”
KYPROLIS is approved in the European Union (EU) for use in combination with lenalidomide and dexamethasone or with dexamethasone alone (Kd) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. The Kd regimen of twice-weekly KYPROLIS administered at 56 mg/m2 and the KRd regimen of twice-weekly KYPROLIS administered at 27 mg/m2 are the first and only therapeutic combinations to demonstrate consistently improved OS versus recent standards of care in two Phase 3 trials in relapsed or refractory multiple myeloma patients (Kd versus bortezomib and dexamethasone [Vd] and KRd versus Rd).
Since its approval in 2012, approximately 80,000 patients worldwide have received KYPROLIS. The KYPROLIS clinical program continues to focus on providing treatment options for physicians and patients for this frequently relapsing and difficult-to-treat cancer.
The international, randomized Phase 3 ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma) trial evaluated KYPROLIS in combination with lenalidomide and dexamethasone, versus lenalidomide and dexamethasone alone, in patients with relapsed or refractory multiple myeloma following treatment with one to three prior regimens. The primary endpoint of the trial was progression-free survival, defined as the time from treatment initiation to disease progression or death. Secondary endpoints included OS, overall response rate, duration of response, disease control rate, health-related quality of life and safety. Patients were randomized to receive KYPROLIS (20 mg/m2 on days 1 and 2 of cycle one, escalating to 27 mg/m2 on days 8, 9, 15 and 16 of cycle one and continuing on days 1, 2, 8, 9, 15 and 16 of subsequent cycles), in addition to a standard dosing schedule of lenalidomide (25 mg per day for 21 days on, seven days off) and low-dose dexamethasone (40 mg per week in four-week cycles), versus lenalidomide and low-dose dexamethasone alone. The study randomized 792 patients at sites in North America, Europe and Israel. The study results were published in the Journal of Clinical Oncology.
The safety data from ASPIRE was consistent with the known safety profile of KYPROLIS. The most common adverse events (greater than or equal to 20 percent) in the KYPROLIS arm were diarrhea, anemia, neutropenia, fatigue, upper respiratory tract infection, pyrexia, cough, hypokalemia, thrombocytopenia, muscle spasms, pneumonia, nasopharyngitis, nausea, constipation, insomnia and bronchitis.
About Multiple Myeloma
Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse.1 It is a rare and very aggressive disease that accounts for approximately one percent of all cancers.2,3 In Europe, approximately 39,000 patients are diagnosed with multiple myeloma each year and 24,000 patient deaths are reported on an annual basis.4