Johnson & Johnson announced FDA approval of Darzalex Faspro (daratumumab and hyaluronidase-fihj) as a single-agent treatment for adult patients with high-risk smoldering multiple myeloma (HR-SMM) on November 6th, 2025. According to a company press release, it is the first and only approved treatment for HR-SMM.
FDA approval was based on findings from the AQUILA study, a randomized, multicenter Phase III study comparing treatment with daratumumab and hyaluronidase-fihj to active monitoring in patients with SMM. According to the release, the treatment demonstrated a significant improvement in the study’s primary endpoint of progression-free survival, reducing the risk of disease progression to active multiple myeloma or death by 51% relative to active monitoring.
SMM is an asymptomatic malignancy that is genomically the same as active multiple myeloma. According to the release, an estimated 50 percent of patients diagnosed with HR-SMM are likely to progress to active disease within two years of diagnosis. Prior to this approval, the standard of care for HR-SMM is active monitoring to track signs of biochemical progression and/or end-organ damage.
“Until now, patients diagnosed with smoldering multiple myeloma only have the option to watch and wait for any active signs of progression to active disease,” said Peter Voorhees, M.D., Atrium Health/Levine Cancer Institute, in the release. “Results from AQUILA demonstrated [daratumumab and hyaluronidase-fihj] significantly delayed disease progression, underscoring the role of early disease intervention for patients with high-risk smoldering multiple myeloma.”
“[Daratumumab and hyaluronidase-fihj] is a foundational therapy in multiple myeloma and illustrates our commitment to improve outcomes for patients at every stage of their disease,” said Jordan Schecter, M.D., Vice President, Research & Development, Multiple Myeloma, Oncology, Johnson & Johnson Innovative Medicine, in the release. “Data from the AQUILA study reinforce the significant impact [daratumumab and hyaluronidase-fihj] continues to have for patients. With today’s approval, patients with HR-SMM will now be able to receive this treatment before they progress to active multiple myeloma, giving us the opportunity to shift the treatment paradigm and bring hope to people who are impacted by this disease.”
Daratumumab and hyaluronidase-fihj is a subcutaneous CD38-directed antibody co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology. According to the release, the treatment had previously received FDA approval for ten indications in multiple myeloma; four of these indications are for frontline treatment in newly diagnosed patients who are either transplant-eligible or ineligible.
