FDA Approves Combination Therapy of CD38 Antibody and Proteasome Inhibitor for Relapsed/Refractory Multiple Myeloma

Today, Amgen and Janssen, a subsidiary of Johnson & Johnson, separately announced that the U.S. FDA has approved two dosing regimens (once weekly and twice weekly) for the combination of Amgen’s Kyprolis (carfilzomib) with Janssen’s Darzalex (daratumumab) plus dexamethasone (DKd), for the treatment of patients with relapsed/refractory multiple myeloma (R/R MM) who have received one to three prior lines of therapy. This marks the first FDA approval of a combination therapy comprising an anti-CD38 antibody and carfilzomib for this patient population.

Multiple myeloma is a blood cancer characterized by multiple remissions and relapses, with worsening patient outcomes upon each recurrence. As the use of immunomodulatory drugs (IMiDs) becomes more widespread following disease progression, the number of patients who develop resistance to these agents and experience continued disease progression despite treatment is likely to increase over time. Therefore, there is a need for IMiD-free treatment regimens for managing disease relapse.

Kyprolis is a proteasome inhibitor that induces the death of multiple myeloma cells by inhibiting proteasome function, leading to the accumulation of abnormal proteins within the cells. Darzalex, developed by Janssen, is a monoclonal antibody targeting CD38; it binds to CD38, which is highly expressed on the surface of multiple myeloma cells, thereby inducing cell death. These two drugs are prominent representatives of proteasome inhibitors and CD38-targeting antibodies, respectively, and both have been approved for the treatment of multiple myeloma.

This approval is based on the Phase 1b clinical trial named EQUULEUS and the Phase 3 clinical trial named CANDOR. CANDOR is the first randomized Phase 3 clinical trial to compare DKd with the combination of Kyprolis and dexamethasone (Kd) in patients with relapsed/refractory multiple myeloma (R/R MM). The study met its primary endpoint, demonstrating a 37% reduction in the risk of disease progression or death for patients receiving DKd compared to those receiving Kd (HR=0.63; 95% CI: 0.464, 0.854; p=0.0014 [one-sided]).

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