The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 6-2 in favor of the benefit-risk profile of Johnson & Johnson’s (J&J) Darzalex Faspro (daratumumab and hyaluronidase-fihj) as a monotherapy for adults with high-risk smoldering multiple myeloma (HR-SMM). ODAC’s positive vote was based on data from the Phase III AQUILA trial, which demonstrated that early intervention with Darzalex Faspro significantly reduced the risk of progression or death compared to active monitoring.¹

Could Darzalex Faspro Redefine Treatment for High-Risk Smoldering Multiple Myeloma?

"Early intervention in high-risk smoldering multiple myeloma demonstrated a reduction in the risk of progression or death," said Sen Zhuang, MD, VP, oncology clinical research, Johnson & Johnson Innovative Medicine, in a press release. "The proactive approach demonstrated in the AQUILA study is an example of Johnson & Johnson's aspiration to get in front of cancer by providing a platform to treat disease before progression to active disease."

AQUILA Study Evaluates Darzalex Faspro vs. Active Monitoring

• The randomized, multicenter AQUILA study compared Darzalex Faspro to active monitoring in 390 patients.
• At the time of enrollment, all patients had been diagnosed with SMM within the past five years and were excluded if they were previously treated with either approved or investigational treatments.
• The primary endpoint of the study was progression-free survival (PFS), defined as progression to active multiple myeloma (MM) as assessed by an independent review committee. Secondary endpoints included overall response rate, PFS on first-line MM treatment, and overall survival (OS).^1,2

Darzalex Faspro Demonstrates 51% Risk Reduction in Progression or Death

• The data, which were presented in The New England Journal of Medicine, show that Darzalex Faspro demonstrated a 51% reduction in the risk of disease progression or death compared to active monitoring (HR: 0.49; 95% CI: 0.36–0.67; P<0.001).
• At five years, PFS was 63.1% in the Darzalex Faspro group compared to 40.8% in the active-monitoring group.
• OS at five years was 93% for patients treated with Darzalex Faspro versus 86.9% in the active-monitoring group.
• The death rate was 7.7% in the treatment group compared to 13.3% in the control arm.
• The most common grade 3 or 4 adverse event (AE) was hypertension, which occurred in 5.7% of patients in the treatment group and 4.6% in the active-monitoring group. While no new safety signals were identified, 5.7% of patients discontinued treatment with Darzalex Faspro due to AEs.³

Regulatory Review May Lead to First Approved Therapy for HR-SMM

In November 2024, J&J submitted regulatory applications to the FDA and EMA based on the AQUILA trial results, stating that if approved, Darzalex Faspro could become the first treatment indicated for high-risk SMM.^1,2 In July 2024, the FDA also approved the treatment in combination with bortezomib, lenalidomide, and dexamethasone for patients with newly diagnosed multiple myeloma who are eligible for an autologous stem cell transplant.⁴

High-Risk SMM: A Silent but Serious Precursor to Multiple Myeloma

According to Cleveland Clinic, smoldering multiple myeloma affects approximately one in every 100,000 people, mostly in individuals over 60 years of age. The median age of diagnosis is between 62 and 67 years of age. Within one year of diagnosis, approximately 10% of individuals with SMM risk developing active MM.⁵

"High-risk smoldering multiple myeloma remains a challenging clinical conundrum with no approved therapies, and earlier intervention may delay or even prevent progression to active multiple myeloma," said Peter Voorhees, MD, Atrium Health / Levine Cancer Institute, Charlotte, NC, in the press release. "We appreciate the balance the committee provided when assessing the risks and benefits of finite treatment at this stage and its recognition of the promise of Darzalex Faspro."

References

1. 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 May 21, 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

2. Johnson & Johnson Submits Regulatory Applications for Darzalex Faspro for High-Risk Smoldering Multiple Myeloma. PharmExec. November 8, 2024. Accessed May 21, 2025. https://www.pharmexec.com/view/johnson-johnson-submits-regulatory-applications-darzalex-faspro-high-risk-smoldering-multiple-myeloma

3. Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma. The New England Journal of Medicine. December 9, 2024. Accessed May 21, 2025. https://www.nejm.org/doi/full/10.1056/NEJMoa2409029

4. FDA Approves Johnson & Johnson’s Darzalex Faspro in Combination with Bortezomib, Lenalidomide, and Dexamethasone for Newly Diagnosed Multiple Myeloma. PharmExec. July 31, 2024. Accessed May 21, 2025. https://www.pharmexec.com/view/fda-approves-johnson-johnson-darzalex-faspro-combination-bortezomib-lenalidomide-dexamethasone-newly-diagnosed-multiple-myeloma

5. Smoldering Multiple Myeloma (SMM). Cleveland Clinic. Accessed May 21, 2025. https://my.clevelandclinic.org/health/diseases/23911-smoldering-multiple-myeloma