FDA Advisory Panel Backs J&J's Darzalex for Smoldering Multiple Myeloma

Johnson & Johnson's Darzalex Faspro has received a favorable recommendation from the FDA's Oncologic Drugs Advisory Committee (ODAC) for the treatment of high-risk smoldering multiple myeloma (SMM), potentially paving the way for the first approved therapy in this indication.

ODAC Vote and Trial Results

The ODAC voted 6-2 in favor of Darzalex Faspro's benefit-risk profile for SMM patients, despite concerns raised by FDA regulators. The recommendation was based on data from the phase 3 Aquila trial, which evaluated the subcutaneous formulation of Darzalex against simple monitoring in high-risk SMM patients.

Key findings from the Aquila trial include:

• A 51% reduction in the risk of SMM progressing to active multiple myeloma compared to surveillance
• A 6-percentage-point difference in overall survival between the two trial arms at five years
• Consistent favorable outcomes across multiple analyses

Regulatory Challenges and Concerns

The FDA raised several questions during the advisory committee meeting, highlighting the complexities of developing treatments for early-stage cancers:

1. Patient selection: More than half of the Aquila trial participants did not meet current high-risk SMM criteria, which were updated after the trial's initiation in 2017.

2. Clinical meaningfulness: The FDA questioned whether delaying progression to active multiple myeloma is sufficient, given that almost all SMM cases eventually progress.

3. Long-term impact: Regulators expressed concerns about potential effects of early SMM treatment on future multiple myeloma therapies and the drug's toxicity profile.

Despite these issues, most panelists were persuaded by the consistent favorable findings and the potential for Darzalex Faspro to extend patients' lives.

Future Considerations

Committee members emphasized the need for careful definition of the eligible patient population in a potential FDA approval. They also called for continued follow-up of the Aquila trial to further understand Darzalex's profile in this groundbreaking indication.

As the pharmaceutical industry continues to explore earlier interventions in cancer treatment, the development and regulatory experience with Darzalex Faspro in SMM highlights the challenges companies face in identifying the right patients and demonstrating meaningful clinical benefits in early-stage disease settings.