Johnson & Johnson announced today the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for approval of a new indication for DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) in combination with bortezomib, lenalidomide and dexamethasone (D-VRd) for the treatment of adult patients with newly diagnosed multiple myeloma (NDMM) for whom autologous stem cell transplant (ASCT) is deferred or who are ineligible for ASCT.
This submission is supported by data from the Phase 3 CEPHEUS study (NCT03652064), 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 evaluated the efficacy and safety of D-VRd compared to bortezomib, lenalidomide and dexamethasone (VRd) for NDMM patients 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 (10-5) of 60.9 percent vs 39.4 percent at a median follow-up of 58.7 months (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.58-3.55; P<0.0001). The sustained MRD-negativity rate favored D-VRd 48.7 percent vs 26.3 percent for VRd (P<0.0001). The study also demonstrated that D-VRd significantly reduced the risk of progression or death by 43 percent (hazard ratio, 0.57; 95% CI, 0.41-0.79; P<0.0005) vs VRd and achieved an overall complete response (CR) or better rate of 81.2 percent with D-VRd vs 61.6 percent with VRd (P<0.0001). The overall safety profile of D-VRd was consistent with the known safety profiles for DARZALEX FASPRO and VRd.
“DARZALEX FASPRO-based therapies continue to be at the forefront of multiple myeloma research. We’re encouraged that the FDA Oncologic Drugs Advisory Committee recently voted in favor of MRD-negativity as an acceptable endpoint in multiple myeloma trials. CEPHEUS is the first registrational study with a primary endpoint of MRD-negativity filed by Johnson & Johnson in multiple myeloma,” said Craig Tendler, M.D., Vice President, Late Clinical Development and Global Medical Affairs, Innovative Medicine, Johnson & Johnson. “The data from CEPHEUS add to the body of evidence for DARZALEX FASPRO 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 CEPHEUS was presented as a late-breaking oral presentation (Abstract #OA-63) at the 2024 International Multiple Myeloma Society (IMS) Annual Meeting.
