Janssen, a Johnson & Johnson company, 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 daratumumab as a monotherapy for patients with high-risk smoldering multiple myeloma. The applications are supported by data from the Phase 3 AQUILA study, which investigated daratumumab subcutaneous (SC) formulation versus active monitoring in this patient population. If approved, daratumumab would represent the first approved treatment for this early stage of multiple myeloma.
Addressing an Unmet Need in Smoldering Multiple Myeloma
Smoldering multiple myeloma is a precursor to active multiple myeloma, characterized by the presence of abnormal plasma cells in the bone marrow without overt symptoms. Approximately 15% of newly diagnosed multiple myeloma cases are classified as smoldering, and half of those with high-risk disease progress to active myeloma within two years. Currently, the standard of care involves active monitoring until the development of active disease and end-organ damage, at which point treatment is initiated. However, recent evidence suggests that earlier therapeutic intervention may benefit patients at high risk of progression.
"There remains an unmet need for early interventions and treatments that are both effective and well tolerated in people living with smouldering 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. "Daratumumab 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 smouldering multiple myeloma, potentially shifting the treatment paradigm."
The AQUILA Study: Daratumumab Monotherapy in High-Risk Smoldering Myeloma
The AQUILA study (NCT03301220) is a randomized, multicenter Phase 3 trial evaluating daratumumab SC versus active monitoring in 390 patients with high-risk smoldering multiple myeloma. The primary endpoint is progression-free survival (PFS), with secondary endpoints including time to progression (TTP), overall response rate (ORR), and overall survival (OS). Patients diagnosed with smoldering multiple myeloma within the past five years were eligible, provided they had no prior exposure to treatments for smoldering or active multiple myeloma. The first data from the AQUILA study, evaluating the safety and efficacy of 3 years fixed duration daratumumab SC compared to active monitoring in participants with high-risk smouldering multiple myeloma, will be presented at the 2024 American Society of Hematology (ASH) Annual Meeting, taking place in San Diego from December 7-10.
About Daratumumab
Daratumumab is a CD38-directed antibody that binds to the CD38 protein, which is highly expressed on multiple myeloma cells. Daratumumab inhibits tumor cell growth and induces myeloma cell death. Since its launch, daratumumab has become a foundational therapy in the treatment of multiple myeloma, having been used in the treatment of more than 548,000 patients worldwide. Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology. Data from ten Phase 3 clinical trials have demonstrated that daratumumab-based regimens significantly improve progression-free survival and/or overall survival in both frontline and relapsed settings.
Multiple Myeloma: An Incurable Blood Cancer
Multiple myeloma is an incurable blood cancer affecting plasma cells in the bone marrow. In multiple myeloma, malignant plasma cells proliferate, accumulate, crowd out normal blood cells, and cause bone destruction and other complications. In the European Union, it was estimated that more than 35,000 people were diagnosed with multiple myeloma in 2022, and more than 22,700 patients died. While some patients are asymptomatic initially, others experience bone fracture or pain, low red blood cell counts, fatigue, high calcium levels, infections, or kidney damage.
