On the heels of Johnson and Johnson (J&J) receiving a high profile FDA approval with Caplyta for major depressive disorder, the manufacturer announced another significant approval for Darzalex Faspro as a single agent treatment for adult patients suffering from high-risk multiple myeloma (HR-SMM).¹

The regulatory action is noteworthy as Darzalex Faspro becomes the first and only treatment to gain FDA approval for patients with HR-SMM and may allow for earlier therapeutic intervention that prevents the disease from progressing to active multiple myeloma.

“Darzalex Faspro 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. “Data from the Aquila study reinforce the significant impact Darzalex Faspro 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.”¹

What is Darzalex Faspro’s approval based on?

Darzalex Faspro is a CD38-directed antibody that has previously been approved by the FDA for several indications in multiple myeloma, with three in the frontline treatment of newly diagnosed patients who are transplant eligible or ineligible.²

According to a press release from J&J, FDA’s latest approval of Darzalex Faspro is based on findings from the Aquila study. Aquila, which was the largest Phase III trial in patients with HR-SMM, compared the efficacy and safety of Darzalex Faspro to active monitoring.

In the Aquila study, Darzalex Faspro demonstrated significant improvements in the primary endpoint of progression-free survival (PFS), reducing the risk of disease progression or death by 51% compared to active monitoring.¹

FDA’s approval of Darzalex Faspro followed a 6-2 vote in May by the FDA’s Oncologic Drugs Advisory Committee in favor of Darzalex Faspro’s benefit-risk profile as a single agent treatment for patients with HR-SMM.³

What were Darzalex Faspro’s results from the Phase III Aquila trial?

Results from the Phase III Aquila trial showed that 63.1% patients administered Darzalex Faspro did not progress to active myeloma at the five-year mark, compared to 40.7% in the active monitoring group, at a follow-up median of 65 months.¹

Currently, most physicians employ the Mayo 2018 criteria (20/2/20) to assess risk status in patients with HR-SMM. In a post hoc analysis of the Aquila study, 41% of patients met the Mayo 2018 HR-SMM classification, with median PFS not reached in patients who were administered Darzalex Faspro.¹

Additionally, participants treated with Darzalex Faspro in the Aquila achieved a response rate of 63.4% compared to just 2% with active monitoring. In terms of safety, adverse events (AEs) observed in the Aquila study remained consistent with previous studies of Darzalex Faspro. The most common AEs in patients who received Darzalex Faspro including:

• Upper respiratory tract infection
• Musculoskeletal pain
• Fatigue
• Diarrhea
• Rash
• Sleep disorder
• Sensory neuropathy
• Injection site reactions

Results from the Aquila study were presented at the 2024 American Society of Hematology Annual Meeting, along with being simultaneously published in The New England Journal of Medicine.² In December 2025, a subgroup analysis from the Aquila study evaluating Darzalex Faspro’s efficiency and safety is expected to be presented at the 2025 American Society of Hematology Annual Meeting in Orlando.¹

Sources

1. DARZALEX FASPRO® is the first and only treatment approved by the U.S. FDA for patients with high-risk smoldering multiple myeloma Johnson and Johnson November 6, 2025. Accessed November 7, 2025. https://www.jnj.com/media-center/press-releases/darzalex-faspro-is-the-first-and-only-treatment-approved-by-the-u-s-fda-for-patients-with-high-risk-smoldering-multiple-myeloma

2. Sonneveld P., et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med 2024; 390:301-313. DOI: 10.1056/NEJMoa2312054. January 25, 2024. Accessed November 7, 2025.

3. U.S. FDA Oncologic Drugs Advisory Committee votes in favor of the benefit-risk profile of DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) for high-risk smoldering multiple myeloma. PR Newswire. May 20, 2025. Accessed November 7, 2025. https://prnmedia.prnewswire.com/news-releases/us-fda-oncologic-drugs-advisory-committee-votes-in-favor-of-the-benefit-risk-profile-of-darzalex-faspro-daratumumab-and-hyaluronidase-fihj-for-high-risk-smoldering-multiple-myeloma-302461151.html