J&J Seeks U.S. and EU Approval for DARZALEX FASPRO®/DARZALEX® as Subcutaneous Monotherapy for High-Risk Smoldering Multiple Myeloma

Johnson & Johnson has recently submitted regulatory applications to both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for a new indication of their drug DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) in the U.S. and DARZALEX® subcutaneous (SC) formulation in the European Union (EU). This request stems from promising data gathered in the ongoing Phase 3 AQUILA study, which is scrutinizing the efficacy of DARZALEX FASPRO® as a standalone treatment for adults with high-risk smoldering multiple myeloma.

Smoldering multiple myeloma is an early stage of multiple myeloma where abnormal cells are present in the bone marrow, but patients typically do not show symptoms. This condition represents about 15% of all newly diagnosed multiple myeloma cases, with half of the high-risk patients progressing to active multiple myeloma within two years. Current medical practice involves monitoring these patients rather than providing active treatment until the disease advances. However, recent studies suggest that early intervention may benefit those at high risk of progression to active disease.

Dr. Yusri Elsayed, Global Therapeutic Area Head, Oncology, Innovative Medicine at Johnson & Johnson, emphasized the need for effective and well-tolerated treatments for patients with high-risk smoldering multiple myeloma. He noted that DARZALEX has already transformed the treatment landscape for multiple myeloma and could potentially set a new standard for treating patients with high-risk smoldering multiple myeloma if the new indication is approved.

The initial findings from the AQUILA study, which compares the safety and effectiveness of DARZALEX FASPRO® against active monitoring, are scheduled to be presented at the American Society of Hematology (ASH) Annual Meeting in December 2024. This study involves 390 participants and aims to assess the drug’s impact on progression-free survival, time to progression, overall response rate, and overall survival. Participants were diagnosed with smoldering multiple myeloma in the past five years and had not received prior treatments for multiple myeloma.

Smoldering multiple myeloma is characterized by an increased number of abnormal plasma cells in the bone marrow and elevated monoclonal protein levels in the blood. Although the patients do not yet display symptoms like end-organ damage, the condition can progress to active multiple myeloma, a serious blood cancer affecting plasma cells in the bone marrow. Multiple myeloma is the second most common blood cancer globally and remains incurable, with an estimated 35,000 new diagnoses and over 12,000 deaths expected in the U.S. in 2024 alone. The five-year survival rate for multiple myeloma patients is approximately 59.8%.

DARZALEX FASPRO®, approved by the FDA in May 2020, is used to treat multiple myeloma in nine different indications, including frontline treatments for newly diagnosed patients. It is the only subcutaneous CD38-directed antibody approved for this purpose. The intravenous formulation, DARZALEX®, initially received FDA approval in November 2015 and is available for eight indications. DARZALEX®-based treatments have been administered to over 518,000 patients globally.

In conclusion, the approval of DARZALEX FASPRO® for high-risk smoldering multiple myeloma could provide a groundbreaking treatment option, potentially altering the management of this precursor to multiple myeloma by addressing the disease before it progresses to more severe stages.