US pharmaceutical major Johnson & Johnson has officially submitted regulatory applications to both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The applications aim to provide a new indication for the combination of daratumumab and hyaluronidase, which is marketed as Darzalex Faspro in the United States, and for Darzalex in its subcutaneous form within the European Union. The application seeks to secure approval for Darzalex Faspro as a standalone treatment for patients with high-risk, smoldering multiple myeloma.

Smouldering multiple myeloma represents an early stage of the disease, characterized by the presence of abnormal plasma cells in the bone marrow, yet it remains asymptomatic prior to the onset of active multiple myeloma. Smouldering multiple myeloma accounts for approximately 15% of newly diagnosed cases. Among these, nearly 50% of high-risk smoldering cases progress to active disease within a two-year timeframe. The prevailing approach to managing smoldering multiple myeloma emphasizes vigilant observation over immediate intervention. Recent research indicates that patients identified as high-risk could gain significant advantages from receiving intervention at an earlier stage. 

Dr. Yusri Elsayed, Global Therapeutic Area Head of Oncology at Johnson & Johnson, emphasized the critical gap in early interventions and treatments for individuals with smoldering multiple myeloma who are at a heightened risk of progressing to active myeloma. The need for solutions that are both effective and well tolerated remains urgent. 

"Darzalex has revolutionized the standard of care for multiple myeloma. With recent submissions to the FDA and EMA, this therapy stands on the brink of becoming the first approved treatment for patients with high-risk smoldering multiple myeloma, which could significantly alter the treatment landscape,” Dr. Elsayed said.

The regulatory submissions rely on data derived from the ongoing Phase 3 AQUILA study, which investigates the efficacy and safety of Darzalex Faspro as a standalone treatment for high-risk smoldering multiple myeloma in comparison to active monitoring. Researchers conducted a recent study with 390 participants to evaluate progression-free survival as the primary endpoint. Additionally, it examines secondary outcomes, including time to progression, overall response rate, and overall survival. 

The upcoming American Society of Haematology (ASH) Annual Meeting in San Diego, scheduled for December 7–10, 2024, will showcase the initial findings from AQUILA. We anticipate that these findings will illuminate the potential benefits of Darzalex Faspro in delaying disease progression.

The FDA specifically approved Darzalex Faspro in 2020 for the treatment of multiple myeloma. It stands out as the sole subcutaneous CD38-directed antibody available for this condition. Johnson & Johnson said that it is taking significant steps to broaden its indications, demonstrating a strong commitment to meeting the needs of high-risk patients through early intervention options that have the potential to change the trajectory of their disease.