FDA Approves J&J's Darzalex as First Treatment for Smoldering Multiple Myeloma

The U.S. Food and Drug Administration (FDA) has granted approval to Johnson & Johnson's Darzalex subcutaneous formulation for the treatment of high-risk smoldering multiple myeloma (SMM), marking a significant milestone in the management of this precursor condition to multiple myeloma (MM). This decision represents the first-ever approved treatment for SMM, offering a new option for patients who previously could only be monitored for disease progression.

Breakthrough in Myeloma Management

Darzalex, a CD38 antibody, has demonstrated its efficacy in delaying the progression of SMM to active MM. The approval was based on the results of the phase 3 Aquila trial, which showed that Darzalex Faspro significantly reduced the risk of disease progression or death by 51% compared to standard monitoring. Patients treated with Darzalex did not reach the median progression-free survival time, while those in the control group had a median result of 41.5 months.

Dr. Richard Pazdur, who leads the FDA's Oncology Center of Excellence, played a key role in the review process. The decision follows a recommendation from an external advisory committee, which was convinced by the clear trend toward improved survival in the Aquila trial data.

Addressing Concerns and Future Implications

The approval of Darzalex for SMM has not been without controversy. Dr. Vinay Prasad, now the FDA's chief medical and scientific officer and director of the Center for Biologics Evaluation and Research, had previously criticized the proposed use of Darzalex in SMM. His concerns centered on the lack of patient exposure to Darzalex as a subsequent treatment in the control arm of the Aquila trial.

Despite these initial reservations, the approval suggests a more holistic approach to drug evaluations at the FDA. This development is seen as a positive sign for other potential treatments in the pipeline, such as Arcellx and Gilead Sciences' BCMA CAR-T therapy, anito-cel, which is seeking accelerated approval based on phase 2 trial data.

Market Impact and Patient Benefits

The FDA's decision aligns with that of European regulators, who approved Darzalex for SMM in July. This approval opens up a new market for Johnson & Johnson, with an estimated 15% of the 35,000 new myeloma diagnoses in the U.S. in 2024 classified as SMM. Importantly, about 50% of high-risk SMM cases are likely to progress to active MM within two to three years, underscoring the potential impact of early intervention with Darzalex.

For patients with SMM, this approval represents a paradigm shift in treatment strategy. Instead of anxious waiting and monitoring, there is now an active treatment option that could significantly delay the onset of symptomatic multiple myeloma, potentially improving long-term outcomes and quality of life for those at high risk of disease progression.