Johnson & Johnson submits application to the European Medicines Agency for DARZALEX (daratumumab)-based quadruplet therapy for the treatment of patients with transplant-eligible, newly diagnosed multiple myeloma

Janssen-Cilag International NV, a Johnson & Johnson company, announced the submission of a Type II variation application to the European Medicines Agency (EMA). The submission is seeking approval for an indication extension of DARZALEX (daratumumab) subcutaneous (SC) formulation in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) for the treatment of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant (ASCT).

“Despite significant advances, multiple myeloma remains an incurable disease affecting more than 35,000 people each year in Europe alone,” said Edmond Chan, MBChB, M.D. (Res), EMEA Therapeutic Area Lead Haematology, Johnson & Johnson Innovative Medicine. “We know response to first-line therapy is vital to improve patients’ long-term outcomes, which is why we are proud of today’s submission and the potential of this daratumumab subcutaneous-based, quadruplet therapy to achieve deep and durable responses in patients with newly diagnosed multiple myeloma.”

The submission to the EMA is supported by data from the Phase 3 PERSEUS (NCT03710603) study, evaluating D-VRd induction and consolidation therapy, ASCT, and daratumumab with lenalidomide (D-R) maintenance therapy, compared to VRd, ASCT and R maintenance. Results from the primary analysis showed that the study met its primary endpoint of progression-free survival (PFS), with a significant reduction in the risk of disease progression or death of 58 percent at a median follow-up of 47.5 months (Hazard Ratio [HR], 0.42; 95 percent Confidence Interval [CI] 0.30-0.59; P<0.0001), compared to the control arm. Treatment with D-VRd and ASCT followed by D-R maintenance also significantly increased the depth of response, with higher rates of complete response (CR) or better, stringent CR (sCR) and minimal residual disease (MRD) negativity compared to treatment with VRd, ASCT and R maintenance. Overall, 64 percent of patients who entered the maintenance phase in the D-VRd arm were able to discontinue treatment with daratumumab SC after achieving a CR or better and sustained MRD negativity, for 12 months or longer, following at least two years of D-R maintenance in accordance with the trial protocol. The overall safety profile of D-VRd followed by D-R maintenance was consistent with the known safety profiles for daratumumab SC, VRd and R.

Data from the PERSEUS study were featured as a late-breaking oral presentation at the 2023 American Society of Hematology (ASH) Annual Meeting and were simultaneously published in The New England Journal of Medicine.

“The impressive results from the PERSEUS study highlight the potential of this daratumumab subcutaneous-based regimen to transform patient outcomes and provide an effective therapy option in newly diagnosed, transplant-eligible multiple myeloma,” said Craig Tendler, M.D., Vice President, Clinical Development, Diagnostics, and Global Medical Affairs, Johnson & Johnson Innovative Medicine. “We are committed to advancing innovative regimens, such as D-VRd, as we strive towards the elimination of this complex disease. We now look forward to working with the EMA on the review of this submission.”