For the first time, patients with abnormal cells detected in their bone marrow have a treatment option before the condition develops into multiple myeloma.
The FDA has approved Johnson & Johnson’s Darzalex subcutaneous formulation to treat patients with smoldering multiple myeloma (SMM) that is at a high risk of developing into multiple myeloma.
Before Thursday’s approval, doctors could only monitor patients with SMM, which is an asymptomatic intermediate disease state, in hopes of catching early signs of the condition’s development into cancerous MM.
More than 35,000 people were estimated to be diagnosed with myeloma in the U.S. in 2024, with about 15% of new diagnoses classified as SMM, according to J&J. About 50% of high-risk SMM cases are likely to progress into active MM within two to three years.
The approval was based on results from a phase 3 trial called Aquila, which showed that Darzalex Faspro significantly delayed disease progression to MM or death by 51% versus basic monitoring. The median progression-free survival time was not reached in the Darzalex arm, versus a median result of 41.5 months in the control group.
The FDA initially had hesitations about the company’s application, raising doubts about whether more mature patient survival data were needed to determine Darzalex’s benefit-risk profile for an asymptomatic precursor condition, especially since the CD38 antibody is well established as a powerful treatment for multiple myeloma.
In approving Darzalex, the FDA followed the recommendation of an external advisory committee. Advisors to the agency said they were convinced by results from the Aquila trial, including a preliminary but clear sign of a trend toward improved survival, although they still urged J&J to follow the study to further characterize Darzalex’s profile in SMM.
A step ahead of the FDA, European regulators had already approved Darzalex in SMM in July.
The approval of Darzalex in SMM offers drugmakers some relief, because the drug’s proposed use had previously drawn criticism from Vinay Prasad, M.D., before he became the FDA’s chief medical and scientific officer as well as director of the Center for Biologics Evaluation and Research. Prasad has been known as a proponent of overall survival serving as the most important endpoint to determine a drug’s approvability. In a December 2024 post, he criticized the lack of patient exposure to Darzalex as a subsequent treatment for patients in Aquila’s control arm.
Although Darzalex’s review fell within the purview of Richard Pazdur, M.D., who leads the FDA’s Oncology Center of Excellence, Prasad’s chief medical and scientific officer title at the agency theoretically could give him power to intervene.
The Darzalex approval in SMM serves as proof that Prasad is “taking a more holistic approach to some approvals,” Everecore ISI analyst Cory Kasimov wrote in a Thursday note.
In the MM field, Kasimov viewed the nod as a positive sign for Arcellx and Gilead Sciences’ upcoming accelerated approval bid for their BCMA CAR-T therapy anito-cel. Since the partners plan to seek accelerated approval based on the phase 2 IMMagine-1 trial, the drug won’t have randomized OS data to back its case. As a cell therapy, anito-cel lands with Prasad’s department, with expected meaningful input from Pazdur’s team as well.