Johnson & Johnson extended filing at EMA for Darzalex (daratumumab subcutaneous) + R-VDd for 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) 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 (NDMM).

“While we’ve seen significant progress in multiple myeloma treatment, there continues to be a tremendous opportunity to improve frontline therapies and ensure we are providing patients with better long-term outcomes,” said Edmond Chan, MBChB, M.D. (Res), EMEA Therapeutic Area Lead Hematology, Innovative Medicine, Johnson & Johnson. “The potential of this daratumumab subcutaneous-based regimen to transform outcomes for people with newly diagnosed multiple myeloma is incredibly promising, and today’s submission builds on our portfolio of Phase III studies aimed at elevating the standard of care for all patients in the frontline treatment setting.”

This submission is supported by data from the Phase III CEPHEUS study, which showed 60.9 percent of patients achieved minimal residual disease (MRD)-negativity with D-VRd and the risk of progression or death was reduced by 43 percent. The CEPHEUS study (NCT03652064), evaluated the efficacy and safety of D-VRd compared to VRd for NDMM patients who are transplant ineligible or for whom ASCT was not planned as initial therapy (transplant ineligible or deferred). The D-VRd regimen increased depth and durability of responses compared to VRd, including the primary endpoint of overall MRD-negativity rate (10 ) of 60.9 percent vs 39.4 percent at a median follow-up of 58.7 months (Odds Ratio [OR], 2.37; 95 percent confidence interval [CI], 1.58-3.55; p<0.0001). The sustained MRD-negativity rate favoured D-VRd (48.7 percent vs 26.3 percent; p<0.0001). The study also demonstrated that D-VRd significantly reduced the risk of progression or death by 43 percent (Hazard Ratio [HR], 0.57; 95 percent CI, 0.41-0.79; p=0.0005) vs VRd and achieved an overall complete response (CR) or better rate of 81.2 percent vs 61.6 percent with VRd (p<0.0001).

The overall safety profile of D-VRd was consistent with the known safety profiles for daratumumab and VRd.¹ The most common (>10 percent) Grade 3/4 haematologic and non-haematologic adverse events with D-VRd vs VRd were neutropenia (44.2 percent vs 29.7 percent), thrombocytopenia (28.4 percent vs 20.0 percent), anaemia (13.2 percent vs 11.8 percent), peripheral neuropathies (8.1 percent vs 8.2 percent), diarrhoea (12.2 percent vs 9.2 percent), and COVID-19 (11.2 percent vs 4.6 percent).¹

“Daratumumab SC-based therapies continue to be at the forefront of multiple myeloma research. CEPHEUS is the first registrational study with a primary endpoint of MRD-negativity, supported by key secondary endpoints such as progression-free survival, filed by Johnson & Johnson in multiple myeloma,” said Craig Tendler, M.D., Vice President, Clinical Development, Diagnostics, and Global Medical Affairs, Innovative Medicine, Johnson & Johnson. “The data from CEPHEUS add to the body of evidence for daratumumab SC in newly diagnosed multiple myeloma and, together with the results of the PERSEUS study, demonstrate the potential benefit of this quadruplet regimen for newly diagnosed patients, regardless of transplant eligibility.”Data from the CEPHEUS study was presented as a late-breaking oral presentation (LBA –1) at the 2024 International Multiple Myeloma Society (IMS) Annual Meeting.¹