The US Food and Drug Administration (FDA) has approved Johnson & Johnson’s DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) as a single agent treatment for adult patients with high-risk smoldering multiple myeloma (HR-SMM) -— marking it as the first and only approved treatment for this condition.

The decision is based on results from the Phase 3 AQUILA study, the largest clinical trial to date in HR-SMM, which compared DARZALEX FASPRO with active monitoring, also known as “watch and wait.” The study demonstrated a significant improvement in the primary endpoint of progression-free survival (PFS), with DARZALEX FASPRO reducing the risk of disease progression to active multiple myeloma or death by 51 percent compared to active monitoring, according to the International Myeloma Working Group (IMWG) diagnostic criteria for multiple myeloma.

This milestone follows the May 2025 FDA Oncologic Drugs Advisory Committee (ODAC) vote in favour of the benefit–risk profile of DARZALEX FASPRO for this indication.

Smoldering multiple myeloma (SMM) is an asymptomatic malignancy that is genomically the same as active multiple myeloma and where these abnormal cells can be detected in the bone marrow.  An estimated 50 percent of patients diagnosed with HR-SMM are likely to progress to active disease within two years of diagnosis. Currently, the standard of care for HR-SMM is active monitoring to track signs of biochemical progression and/or end-organ damage. Recent evidence suggests that people at high-risk of progressing to active multiple myeloma could benefit from earlier therapeutic intervention.

Peter Voorhees, Atrium Health/Levine Cancer Institute, Charlotte, N.C., said, "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. Results from AQUILA demonstrated DARZALEX FASPRO significantly delayed disease progression, underscoring the role of early disease intervention for patients with high-risk smoldering multiple myeloma."

Jordan Schecter, Vice President, Research & Development, Multiple Myeloma, Oncology, Johnson & Johnson Innovative Medicine, noted that the approval of DARZALEX FASPRO reinforces the company’s ongoing commitment to improving patient outcomes across all stages of multiple myeloma.

"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,” he said.

DARZALEX FASPRO first received FDA approval in May 2020 and is now authorised for ten indications in multiple myeloma, including four frontline uses for newly diagnosed patients, whether they are eligible for transplant or not. It remains the only subcutaneous CD38-directed antibody approved for the treatment of multiple myeloma. The therapy is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), utilising Halozyme’s ENHANZE drug delivery technology to facilitate subcutaneous administration.