Johnson & Johnson Submits Regulatory Applications for Darzalex Faspro for High-Risk Smoldering Multiple Myeloma

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Johnson & Johnson (J&J) has submitted regulatory applications to the FDA and EMA for the approval of Darzalex Faspro (daratumumab and hyaluronidase-fihj) in the United States and subcutaneous formulation in the EU as monotherapy for high-risk smoldering multiple myeloma (SMM). According to the company, the submissions are based on data from the Phase III Aquila trial, which is currently evaluating Darzalez Faspro as an early intervention treatment for the disease.¹

“There remains an unmet need for early interventions and treatments that are both effective and well tolerated in people living with smoldering multiple myeloma at high-risk of progressing to active multiple myeloma,” said Yusri Elsayed, MD, MHSc, PhD, global therapeutic area head, oncology, innovative medicine, Johnson & Johnson, in a press release. “Darzalex has changed the standard of care in multiple myeloma, and with these submissions to the FDA and EMA, this therapy could become the first approved treatment for patients with high-risk smoldering multiple myeloma, potentially shifting the treatment paradigm.”

The randomized, multicenter AQUILA trial enrolled 390 patients with high-risk SMM. The primary endpoint of the study is progression-free survival (PFS), with secondary endpoints that include time to progression, overall response rate, and overall survival. All patients involved with the trial were diagnosed with SMM at least five years before the start of the study and weren’t included if they had prior exposure to approved or investigational treatments for SMM. The data are expected to be presented at the 2024 American Society of Hematology Annual Meeting next month.¹

Back in July, the FDA approved Darzalex Faspro in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) for patients with newly diagnosed multiple myeloma (NDMM) who are eligible for an autologous stem cell transplant. In this indication, the therapy can be administered right after diagnosis and could potentially lead to significantly improved outcomes for NDMM patients. The approval was based on positive results from the Phase III PERSEUS study, which compared D-VRd induction and consolidation therapy to the traditional VRd regimen in transplant-eligible NDMM patients.²

"Multiple myeloma has a highly varied clinical course among patients and in each individual patient, and there is a continued need for innovation and therapies that employ different targets and combinations to provide patients with treatment options at diagnosis and throughout the course of their disease," said Amrita Y. Krishnan, MD, professor, director, Judy and Bernard Briskin Multiple Myeloma Center, City of Hope, in a press release. "The efficacy data supporting this new quadruplet regimen, combined with its established safety and tolerability profile, provide compelling evidence that adding D-VRd upon initial diagnosis as compared to VRd can deepen responses and prolong remissions in the context of autologous stem cell transplantation."²

SMM affects about 15% of new multiple myeloma cases, and those with high-risk SMM face a 50% likelihood of progressing to active disease within two years. Currently, high-risk SMM is generally managed through observation until signs of active multiple myeloma appear, but emerging evidence suggests early intervention could benefit patients at high risk.¹ According to the Cleveland Clinic, SMM typically affects people over 60 years of age, with a median diagnosis between 62 and 67 years of age.³

J&J stated that if the treatment is approved, Darzalex Faspro could become the first treatment indicated for high-risk SMM, potentially transforming the current management approach.¹

References

1. Johnson & Johnson submits applications in the U.S. and EU seeking approval of DARZALEX FASPRO® / DARZALEX® as subcutaneous monotherapy for high-risk smoldering multiple myeloma. J&J. November 8, 2024. Accessed November 8, 2024. https://www.jnj.com/media-center/press-releases/johnson-johnson-submits-applications-in-the-u-s-and-eu-seeking-approval-of-darzalex-faspro-darzalex-as-subcutaneous-monotherapy-for-high-risk-smoldering-multiple-myeloma 

2. FDA Approves Johnson & Johnson’s Darzalex Faspro in Combination with Bortezomib, Lenalidomide, and Dexamethasone for Newly Diagnosed Multiple Myeloma. PharmExec. July 31, 2024. Accessed November 8, 2024.

3. Smoldering Multiple Myeloma (SMM). Cleveland Clinic. Accessed November 8, 2024. https://my.clevelandclinic.org/health/diseases/23911-smoldering-multiple-myeloma