Darzalex receives positive EMA Committee opinion for high-risk smouldering multiple myeloma: Janssen-Cilag International

SMM is an asymptomatic intermediate disease state of multiple myeloma where abnormal cells can be detected in the bone marrow. The current standard of care (SOC) for SMM, even in high-risk cases, is active monitoring (or “Watch and Wait”) to track for signs of biochemical progression and/or end-organ damage. This means therapeutic intervention is only offered when the disease progresses.

“The positive recommendation from the CHMP marks an important step towards addressing the needs of people living with high-risk smouldering multiple myeloma,” said Ester in’t Groen, EMEA Therapeutic Area Head Haematology, Johnson & Johnson Innovative Medicine. “Early disease intervention with daratumumab has the potential to reduce the risk of progression to active multiple myeloma or death by 51 percent for patients with high-risk disease. Pending European Commission approval, patients and physicians will have an option to treat high-risk smouldering multiple myeloma, with the aim to intercept this complex blood cancer before it develops into active disease and importantly, before end-organ damage occurs.”

The CHMP recommendation is supported by data from the Phase 3 AQUILA study ( NCT03301220 ), evaluating the efficacy and safety of fixed-duration monotherapy daratumumab SC compared with active monitoring in those with high-risk SMM. Johnson & Johnson also submitted a supplemental Biologics License Application to the U.S. Food and Drug Administration seeking approval of a new indication for daratumumab SC for the treatment of adult patients with high-risk SMM, based on the Phase 3 AQUILA data, on 8th November 2024. The first data from the study were previously presented at the 2024 American Society of Hematology (ASH) Annual Meeting and simultaneously published in the New England Journal of Medicine. Daratumumab is currently approved in nine indications for multiple myeloma, five of which are in the frontline setting.

“Daratumumab has become a foundational treatment across all stages of multiple myeloma, and we are on a mission to continue to evolve the treatment paradigm to reach those with high-risk smouldering multiple myeloma who may benefit from proactive earlier intervention,” said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine. “Today’s positive CHMP opinion marks positive scientific progress towards this goal and reinforces our vision of eliminating multiple myeloma.”

In August 2012, Janssen Biotech, Inc., a Johnson & Johnson company, and Genmab A/S entered a worldwide agreement, which granted Johnson & Johnson an exclusive licence to develop, manufacture and commercialise daratumumab. Since launch, daratumumab has become a foundational therapy in the treatment of multiple myeloma, having been used in the treatment of more than 618,000 patients worldwide. Daratumumab is a CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma. Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.

CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease. Daratumumab binds to CD38 and inhibits tumour cell growth causing myeloma cell death. Daratumumab may also have an effect on normal cells. Data across ten Phase 3 clinical trials, in both the frontline and relapsed settings, have shown that daratumumab-based regimens resulted in significant improvement in progression-free survival and/or overall survival.