FDA Approves New Kyprolis, Darzalex Combination Regimen

Amgen announced the U.S. Food and Drug Administration (FDA) has approved the expansion of the Kyprolis® (carfilzomib) U.S. prescribing information to include its use in combination with Darzalex® (daratumumab) plus dexamethasone (DKd) in two dosing regimens — once weekly and twice weekly — for the treatment of patients with relapsed or refractory multiple myeloma (R/R MM) who have received one to three previous lines of therapy.

"This expanded approval for Kyprolis demonstrates a leap forward in the treatment paradigm for this complex disease by combining two potent agents in their respective drug classes indicated for patients with relapsed or refractory multiple myeloma," said David M. Reese, M.D., executive vice president of Research and Development at Amgen.

Multiple myeloma is a blood cancer characterized by patterns of remission and relapse. Patient outcomes worsen with each relapse. With the increasing use of frontline immunomodulatory drug based (IMiD) therapies through progression, the number of patients treated with these agents who will progress is likely to increase with time. This creates an emerging need for efficacious lMiD-free regimens upon relapse.

"The DKd regimen provides an important potent triplet option in the setting of relapse following IMiD combination frontline therapy," said Brian G.M. Durie, M.D., chairman, International Myeloma Foundation.

The Phase 3 CANDOR trial was the first Phase 3 randomized trial to compare DKd versus Kyprolis and dexamethasone (Kd) alone in R/R MM patients. The study met its primary endpoint and resulted in a 37% reduction in the risk of disease progression or death in patients receiving DKd (HR=0.63; 95% CI: 0.464, 0.854; p-value [1-sided]=0.0014) compared to Kd alone.

In CANDOR, the safety of DKd was generally consistent with the known safety profiles of the individual agents. The most frequently reported (≥ 20% of subjects in either treatment arm [DKd, Kd]) treatment-emergent adverse events (AEs) included infusion-related reactions, anemia, diarrhea, fatigue, hypertension, pyrexia, upper respiratory tract infection, thrombocytopenia, neutropenia, lymphopenia, cough, dyspnea, and insomnia, headache and back pain. The incidence of treatment-emergent Grade 3 or higher, serious and fatal AEs was higher in the DKd arm compared to the Kd arm. The most common reason for fatal treatment-emergent AEs in both arms was infection. The rate of treatment discontinuation due to AEs was similar in both arms.

The expansion of Kyprolis' prescribing information to include once-weekly dosing of Kyprolis within the DKd regimen was supported by the open-label, multi-cohort Phase 1b EQUULEUS trial, in which the safety and efficacy of DKd was assessed among R/R MM patients using a once-weekly dosing regimen for Kyprolis.

Amgen has submitted marketing applications globally.

Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse. It is a rare and life-threatening disease that accounts for approximately one percent of all cancers. Worldwide, approximately 160,000 people are diagnosed with multiple myeloma each year, and 106,000 patient deaths are reported on an annual basis.

Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed. Kyprolis has been shown to block proteasomes, leading to an excessive build-up of proteins within cells. In some cells, KYPROLIS can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins.