Johnson & Johnson 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) for a new indication. The applications target the treatment of patients with high-risk smoldering multiple myeloma (SMM). In the U.S., the application is for DARZALEX FASPRO, while in the EU, it is for the DARZALEX subcutaneous (SC) formulation.
The submissions are based on data from the Phase 3 AQUILA study (NCT03301220), a randomized, multicenter trial comparing DARZALEX FASPRO to active monitoring in patients with high-risk SMM. The study enrolled 390 patients diagnosed with SMM within the past five years who had not previously received treatment for SMM or multiple myeloma.
AQUILA Study Design and Endpoints
The AQUILA study's primary endpoint was progression-free survival (PFS). Secondary endpoints included time to progression (TTP), overall response rate (ORR), and overall survival (OS). Patients with SMM have elevated levels of abnormal plasma cells in the bone marrow and increased monoclonal protein (M-protein) levels in the blood but lack the end-organ damage symptoms characteristic of active multiple myeloma.
Smoldering Multiple Myeloma Context
Smoldering multiple myeloma represents approximately 15% of newly diagnosed multiple myeloma cases. A significant concern is that about half of those diagnosed with high-risk SMM will progress to active multiple myeloma within two years. Multiple myeloma is a blood cancer affecting plasma cells in the bone marrow. In multiple myeloma, malignant plasma cells proliferate, displacing normal cells in the bone marrow.
Multiple myeloma is the second most common blood cancer globally and remains incurable. In 2024, estimates suggest over 35,000 new diagnoses and over 12,000 deaths from multiple myeloma in the U.S. The five-year survival rate for multiple myeloma is approximately 59.8%. Symptoms can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems, or infections.
