DARZALEX FASPRO® – BiotechReality – Information Intelligence System for Biopharma

Quick Summary New, more effective treatment option available earlier in the disease course. 83% survival rate at 3 years shows durable benefit. Manageable side effects with proper monitoring. Free patient support program available. Johnson & Johnson, a leader in multiple myeloma therapeutics, announced today that the U.S. Food and Drug Administration (FDA) has approved TECVAYLI® (teclistamab-cqyv) plus DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent. This significant approval represents a transformative milestone in multiple myeloma treatment, offering a novel approach for addressing disease progression in an expanding patient population. The combination therapy activates the immune system to target and eradicate myeloma cells expressing BCMA (B-cell maturation antigen), with the potential to become a new standard of care as early as the second-line treatment setting. Unprecedented Clinical Data Drives FDA Approval The FDA's decision was based on compelling results from the Phase 3 MajesTEC-3 trial, an international randomized study that evaluated the safety and efficacy of teclistamab plus daratumumab against investigator's choice of standard-of-care regimens (daratumumab and dexamethasone with either pomalidomide or bortezomib) in patients with relapsed/refractory multiple myeloma. Key Clinical Efficacy Endpoints The MajesTEC-3 study demonstrated statistically significant improvements across all primary and secondary endpoints: Progression-Free Survival (PFS): 83% three-year PFS rate with TECVAYLI plus DARZALEX FASPRO versus 30% in the control arm. 83% reduction in risk of disease progression or death (hazard ratio 0.17; 95% CI 0.12–0.23; P<0.0001). This substantial difference underscores the durable clinical benefit of the combination therapy. Overall Response Rate (ORR): 89.0% ORR with TECVAYLI plus DARZALEX FASPRO compared to 75.3% with standard care (odds ratio 2.65; 95% CI 1.68–4.18). Complete Response or Better (≥CR): 81.8% complete response rate versus 32.1% in the control group (OR 9.56; 95% CI 6.47–14.14). This represents a substantial improvement in achieving deep remissions. Minimal Residual Disease (MRD) Negativity: 58.4% of patients achieved MRD-negativity with the combination therapy versus 17.1% in the control arm (OR 6.78; 95% CI 4.53–10.15; P<0.0001). MRD-negativity is an increasingly recognized predictor of improved patient outcomes. Overall Survival (OS): 83.3% three-year OS rate with TECVAYLI plus DARZALEX FASPRO compared to 65.0% in the control arm. OS benefit favored the combination therapy across all prespecified subgroups (HR 0.46; 95% CI 0.32–0.65; P<0.0001). Read More: FDA Advisory Committee Recommends Johnson & Johnson’s DARZALEX FASPRO® for High-Risk Smoldering Multiple Myeloma Safety Profile and Tolerability The safety analysis revealed that TECVAYLI plus DARZALEX FASPRO maintained a manageable and well-characterized toxicity profile comparable to standard-of-care regimens, supporting its use in broader patient populations: Grade 3/4 Treatment-Emergent Adverse Events (TEAE): Similar incidence rates between the combination therapy (95.1%) and control regimen (96.6%). Most Grade 3/4 events were attributed to cytopenias and infections. Cytokine Release Syndrome (CRS): 60.1% incidence of CRS in TECVAYLI plus DARZALEX FASPRO patients. All cases were Grade 1/2 in severity, indicating excellent tolerability. No treatment discontinuations due to CRS. Standard management protocols effectively controlled symptoms. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): Rare occurrence at 1.1% of patients. Demonstrates improved neurologic tolerability compared to monotherapy data. All ICANS events occurred during the step-up dosing schedule and were manageable. Infections: Any-grade infections: 96.5% with TECVAYLI plus DARZALEX FASPRO vs. 84.1% with control Grade 3/4 infections: 54.1% vs. 43.4% respectively Notably, Grade 3+ infections declined significantly after the first 6 months of treatment with established immunoglobulin supplementation and infection prophylaxis protocols Treatment Discontinuations: Low discontinuation rate due to adverse events: 4.6% versus 5.5% in the control arm Grade 5 (fatal) TEAEs: 7.1% with combination therapy vs. 5.9% with control regimen This favorable safety profile enables broader clinical applicability and supports the potential for use earlier in the treatment paradigm. Read More: European Commission Approves DARZALEX® for Treating High-Risk Smouldering Multiple Myeloma Regulatory Milestone and Strategic Recognition The FDA granted multiple designations highlighting the clinical importance of this approval: Breakthrough Therapy Designation: Recognizing the substantial improvement over existing treatments. Real-Time Oncology Review: Streamlining the review process based on robust clinical evidence. Commissioner's National Priority Voucher (CNPV) Selection: The FDA proactively selected TECVAYLI's supplemental Biologics License Application to participate in the CNPV Pilot Program, underscoring alignment with national priorities for delivering innovative therapies. TECVAYLI's Development Journey and Approval History TECVAYLI represents a significant advance from earlier monotherapy approval: Initial FDA Approval: October 2022 for patients with four or more prior lines of therapy. Dosing Optimization: February 2024 approval for reduced dosing frequency (1.5 mg/kg every two weeks) in patients achieving a complete response or better. Current Approval: March 5, 2026, for second-line use in combination with DARZALEX FASPRO. Global Experience: More than 23,000 patients have been treated worldwide with TECVAYLI since approval. European Authorization: Conditional marketing authorization in August 2022, with subsequent approvals for reduced dosing frequency. Comparison with Standard-of-Care Options The MajesTEC-3 trial compared TECVAYLI plus DARZALEX FASPRO against two established standard-of-care regimens: Daratumumab + Pomalidomide + Dexamethasone (DPd) Daratumumab + Bortezomib + Dexamethasone (DVd) Both control regimens are well-established, widely used options for relapsed/refractory multiple myeloma. The substantial superiority demonstrated in PFS, ORR, complete response rates, and OS against these proven standards underscores the clinical significance of the new approval. Johnson & Johnson Last Modified:

Tag: DARZALEX FASPRO®

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