J&J Seeks EMA Approval for Darzalex SC Quadruplet Regimen in Newly Diagnosed Multiple Myeloma
核心洞察
Janssen-Cilag International NV has submitted a Type II variation application to the EMA for DARZALEX SC in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd).
The submission is supported by the Phase 3 CEPHEUS study, which showed a 60.9% MRD-negativity rate with D-VRd and a 43% reduction in the risk of progression or death.
The CEPHEUS study evaluated D-VRd compared to VRd in NDMM patients ineligible for transplant or for whom ASCT was not planned as initial therapy.
Janssen-Cilag International NV, a Johnson & Johnson company, has submitted 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 (搜索) (NDMM). This submission is based on data from the Phase 3 CEPHEUS study, which demonstrated a significant improvement in minimal residual disease (MRD)-negativity and a reduction in the risk of progression or death. The potential approval could transform outcomes for newly diagnosed multiple myeloma patients.
CEPHEUS Trial Results
The Phase 3 CEPHEUS study (NCT03652064) evaluated the efficacy and safety of D-VRd compared to VRd for NDMM patients who are transplant ineligible or for whom autologous stem cell transplant (ASCT) was not planned as initial therapy. The study revealed that 60.9% of patients achieved MRD-negativity with D-VRd, and the risk of progression or death was reduced by 43% (HR, 0.57; 95% CI, 0.41-0.79; P= 0.0005). The overall complete response (CR) or better rate was 81.2% with D-VRd compared to 61.6% with VRd (p< 0.0001).
Clinical Significance
Edmond Chan, MD, therapeutic lead of hematology for the Europe, Middle East, and Africa region at J&J, stated, "The potential of this daratumumab subcutaneous-based regimen to transform outcomes for people with newly diagnosed multiple myeloma (搜索) is incredibly promising, and today’s submission builds on our portfolio of Phase 3 studies aimed at elevating the standard of care for all patients in the frontline treatment setting."
Craig Tendler, MD, vice president of clinical development, diagnostics, and global medical affairs at Johnson & Johnson, added, "The data from CEPHEUS add to the body of evidence for daratumumab SC in newly diagnosed multiple myeloma (搜索) 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."
Current Treatment Landscape and Unmet Needs
Multiple myeloma (搜索) is an incurable blood cancer affecting plasma cells in the bone marrow. In multiple myeloma, malignant plasma cells proliferate and replace normal cells in the bone marrow. While significant progress has been made in multiple myeloma treatment, there remains a need to improve frontline therapies and ensure better long-term outcomes for patients. The D-VRd combo is already approved for newly diagnosed adult patients eligible for ASCT in the U.S.
Darzalex Mechanism of Action
Daratumumab, the active ingredient in all available Darzalex formulations, works to kill myeloma cells by targeting CD38 (搜索), a protein highly produced by these cancer cells. Its binding to CD38 induces the death of myeloma cells.
Safety Profile
The overall safety profile of D-VRd was consistent with the known safety profiles for daratumumab and VRd. 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).