The U.S. Food and Drug Administration approved Johnson & Johnson’s drug Darzalex Faspro as the first treatment for adults with high-risk smoldering multiple myeloma, a precursor to the blood cancer. The decision marks a shift toward earlier intervention in a disease that typically progresses to active multiple myeloma.

The approval is based on results from the Phase 3 AQUILA trial, which compared Darzalex Faspro—a subcutaneous formulation of daratumumab combined with hyaluronidase—to standard “watch and wait” monitoring. The study enrolled patients with high-risk smoldering multiple myeloma, an asymptomatic condition that shares the same genomic profile as active disease.

After a median follow-up of more than five years, patients receiving Darzalex Faspro had a 51% lower risk of progression to active myeloma or death compared with those under observation, according to Johnson & Johnson. At five years, 63.1% of treated patients had not progressed, versus 40.7% in the monitoring group. The hazard ratio was 0.49, with a confidence interval of 0.36 to 0.67.

Smoldering multiple myeloma accounts for about 15% of the estimated 36,000 new U.S. multiple myeloma cases expected this year. Roughly half of high-risk patients progress to active disease within two years. Until now, the standard of care has been active monitoring for signs of organ damage or biochemical progression.

The AQUILA trial also showed higher response rates among treated patients—63.4% compared with 2% in the control group—and delayed the need for first-line therapy. Median time to initial treatment was not reached in the Darzalex Faspro arm versus 50.2 months for monitoring.

Adverse events were consistent with prior studies of the drug, including upper respiratory infections, fatigue, and injection-site reactions.

Johnson & Johnson said the approval underscores its strategy to expand Darzalex Faspro’s role across the multiple myeloma continuum. “With today’s approval, patients with high-risk smoldering multiple myeloma can receive treatment before progression, shifting the treatment paradigm,” said Jordan Schecter, vice president of oncology research and development.

The AQUILA results were first presented at the 2024 American Society of Hematology meeting and published in The New England Journal of Medicine.