Johnson & Johnson (JNJ) 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 adult patients with high-risk smoldering multiple myeloma (SMM). For the EU, the application is for the subcutaneous (SC) formulation of Darzalex.
The submissions are supported by data from the Phase 3 AQUILA study (NCT03301220), which evaluated Darzalex Faspro as a monotherapy compared to active monitoring in patients with high-risk SMM. The first data from the AQUILA study will be presented at the 2024 American Society of Hematology (ASH) Annual Meeting.
Understanding Smoldering Multiple Myeloma
Smoldering multiple myeloma is an early, asymptomatic precursor to active multiple myeloma. 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 do not exhibit the end-organ damage typically associated with active multiple myeloma. Approximately 15% of newly diagnosed multiple myeloma cases are classified as SMM, and about half of those with high-risk disease progress to active multiple myeloma within two years.
Currently, SMM is generally managed with active monitoring until progression to active multiple myeloma occurs, at which point treatment is initiated. However, recent evidence suggests that early therapeutic intervention may benefit patients at high risk of progression.
AQUILA Study Details
The AQUILA study is a randomized, multicenter Phase 3 trial involving 390 patients with high-risk SMM. The primary endpoint is progression-free survival (PFS), with secondary endpoints including time to progression, overall response rate (ORR), and overall survival (OS). Patients diagnosed with SMM within the past five years were eligible for the study, provided they had no prior exposure to treatments for SMM or multiple myeloma.
Potential Impact of Darzalex Faspro
"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, including four frontline treatments for newly diagnosed patients. Darzalex is the first CD38-directed antibody approved to treat multiple myeloma. Darzalex-based regimens have been used in the treatment of more than 518,000 patients worldwide and more than 68,000 patients in the U.S. alone.
