Johnson & Johnson (J&J) has announced the submission of regulatory applications to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) seeking approval for Darzalex FASPRO® (daratumumab and hyaluronidase-fihj) as a monotherapy for adult patients with high-risk smoldering multiple myeloma. This submission is supported by data from the Phase 3 AQUILA study (NCT03301220), potentially marking a significant advancement in treating this early stage of multiple myeloma. If approved, Darzalex FASPRO® would become the first treatment option for patients with smoldering multiple myeloma at high-risk of developing multiple myeloma, offering a novel approach to treat before the onset of active disease and the occurrence of end organ damage.
Understanding Smoldering Multiple Myeloma
Smoldering multiple myeloma is an early, asymptomatic precursor to active multiple myeloma, characterized by the presence of abnormal plasma cells in the bone marrow and elevated monoclonal protein levels in the blood. Approximately 15% of newly diagnosed multiple myeloma cases are classified as smoldering, with half of the high-risk cases progressing to active myeloma within two years. Currently, the standard approach involves active monitoring until the disease progresses to active myeloma, at which point treatment is initiated.
The AQUILA Study: Daratumumab Monotherapy
The Phase 3 AQUILA study (NCT03301220) is a randomized, multicenter trial evaluating the safety and efficacy of Darzalex FASPRO® compared to active monitoring in patients with high-risk smoldering multiple myeloma. The study enrolled 390 participants diagnosed with smoldering multiple myeloma within the past five years, excluding those with prior treatment for smoldering or active myeloma. The primary endpoint is progression-free survival, with secondary endpoints including time to progression, overall response rate, and overall survival. First data from the AQUILA study will be presented at the 2024 American Society of Hematology (ASH) Annual Meeting.
Potential Impact on Treatment Paradigm
"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, M.D., M.H.Sc., Ph.D. Global Therapeutic Area Head, Oncology, Innovative Medicine, Johnson & Johnson. "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."
About Darzalex FASPRO®
Darzalex FASPRO® (daratumumab and hyaluronidase-fihj) is a subcutaneous formulation of daratumumab, a CD38-directed antibody. It received U.S. FDA approval in May 2020 and is currently approved for nine indications in multiple myeloma. Darzalex FASPRO® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology.
