Janssen-Cilag International NV, a Johnson & Johnson company, has announced the submission of regulatory applications to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) seeking approval of a new indication for DARZALEX® (daratumumab) subcutaneous formulation. The applications aim to secure approval for daratumumab as a monotherapy for the treatment of adult patients with high-risk smoldering multiple myeloma.
The submissions are supported by data from the ongoing Phase 3 AQUILA study (NCT03301220), which is evaluating daratumumab SC as a monotherapy compared to active monitoring in patients with high-risk smoldering multiple myeloma. The first data from the AQUILA study will be presented at the 2024 American Society of Hematology (ASH) Annual Meeting in San Diego.
Understanding Smoldering Multiple Myeloma
Smoldering multiple myeloma is an early precursor to active multiple myeloma, characterized by the presence of abnormal cells in the bone marrow without the presence of symptoms. Approximately 15% of newly diagnosed multiple myeloma cases are classified as smoldering, with half of high-risk cases progressing to active multiple myeloma within two years. Currently, the standard approach involves monitoring patients for signs of biochemical progression or end-organ damage before initiating treatment.
The AQUILA Study: Design and Endpoints
The AQUILA study is a randomized, multicenter Phase 3 trial investigating daratumumab SC versus active monitoring in 390 patients with high-risk smoldering multiple myeloma. Patients diagnosed with smoldering multiple myeloma within the last five years were eligible, provided they had no prior exposure to treatments for smoldering or active multiple myeloma. The primary endpoint is progression-free survival (PFS), with secondary endpoints including time to progression (TTP), overall response rate (ORR), and overall survival (OS).
Daratumumab: A Potential Paradigm Shift
Daratumumab is a CD38-directed antibody that binds to CD38, a surface protein highly expressed on multiple myeloma cells, inhibiting tumor cell growth and inducing myeloma cell death. It has become a foundational therapy in multiple myeloma, with over 548,000 patients treated worldwide since its launch. The subcutaneous formulation of daratumumab is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), utilizing Halozyme's ENHANZE® drug delivery technology.
“There remains an unmet need for early interventions and treatments that are both effective and well tolerated in people living with smouldering 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. “Daratumumab 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 smouldering multiple myeloma, potentially shifting the treatment paradigm.”
If approved, daratumumab will become the first treatment option for patients with smouldering multiple myeloma at high-risk of developing multiple myeloma, offering a novel approach to treat before the onset of active disease and the occurrence of end organ damage.
