Johnson & Johnson (J&J) 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) as a monotherapy for patients with high-risk smoldering multiple myeloma (SMM). This submission is based on data from the Phase 3 AQUILA study and could potentially shift the treatment paradigm for this early precursor to active multiple myeloma.
Addressing an Unmet Need in Smoldering Multiple Myeloma
Smoldering multiple myeloma is characterized by the presence of abnormal plasma cells in the bone marrow without the typical end-organ damage seen in active multiple myeloma. Approximately 15% of newly diagnosed multiple myeloma cases are classified as SMM, with half of high-risk patients progressing to active disease within two years. Currently, the standard of care involves active monitoring until the development of active multiple myeloma. However, recent evidence suggests that early therapeutic intervention in high-risk SMM may improve outcomes.
“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.
The AQUILA Study: Daratumumab Monotherapy in High-Risk SMM
The AQUILA study (NCT03301220) is a randomized, multicenter Phase 3 trial comparing Darzalex FASPRO® to active monitoring in 390 patients with high-risk SMM. The primary endpoint is progression-free survival (PFS), with secondary endpoints including time to progression, overall response rate, and overall survival (OS). Patients diagnosed with SMM within the past five years were eligible, provided they had no prior exposure to treatments for SMM or multiple myeloma.
Darzalex FASPRO®: A CD38-Directed Antibody
Darzalex (daratumumab) is a CD38-directed antibody approved for multiple myeloma treatment. Darzalex FASPRO®, a subcutaneous formulation, was approved by the FDA in May 2020 and is currently indicated for nine multiple myeloma indications. It is co-formulated with recombinant human hyaluronidase PH20, utilizing Halozyme’s ENHANZE® drug delivery technology. Daratumumab binds to the CD38 protein on myeloma cells, triggering cell death through multiple mechanisms.
Implications for Clinical Practice
If approved, Darzalex FASPRO® would be the first therapy indicated for high-risk SMM, offering a proactive approach to delay or prevent progression to active multiple myeloma. The first data from the AQUILA study will be presented at the 2024 American Society of Hematology (ASH) Annual Meeting, providing detailed insights into the efficacy and safety of this potential new treatment option.
