Johnson & Johnson Announces U.S. FDA Approval of TECVAYLI Plus DARZALEX FASPRO For Relapsed/Refractory Multiple Myeloma

Johnson & Johnson announced that the U.S. Food and Drug Administration approved TECVAYLI (teclistamab-cqyv) plus DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) for the treatment of adults 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. TECVAYLI and DARZALEX FASPRO work synergistically to prime and activate the immune system to eradicate myeloma cells that express the BCMA protein. This approval offers a potential new standard of care as early as second line and brings a novel treatment approach for the 40% of patients with multiple myeloma who experience disease relapse.

The approval is based on data from the Phase 3 MajesTEC-3 study, an ongoing, Phase 3 randomized study evaluating the safety and efficacy of teclistamab plus daratumumab versus investigator's choice of daratumumab and dexamethasone with either pomalidomide or bortezomib in patients with RRMM who have received at least one prior line of therapy. TECVAYLI® in combination with DARZALEX FASPRO® demonstrated statistically significant improvements in PFS and OS in patients with RRMM compared to standard treatment after a median follow-up of three years in patients with RRMM. Results show an 83% reduction in the risk of disease progression or death compared to standard regimens (hazard ratio [HR], 0.17; 95%confidence interval [CI], 0.12-0.23; P<0.0001). The three-year PFS rate was 83% compared to 30% in the control arm, underscoring a durable benefit.

The results were presented in December 2025 as a late-breaking oral presentation at the American Society of Hematology (ASH) Annual Meeting with simultaneous publication in The New England Journal of Medicine. Significant improvements compared to SOC were observed across key secondary endpoints, including treatment response rates, minimal residual disease (MRD)-negativity, OS, and time to worsening of symptoms ? revealing the impact of the regimen across varied patient measures.

TECVAYLI® plus DARZALEX FASPRO® showed higher rates of overall response (ORR) (89.0% vs. 75.3%; OR, 2.65; 95% CI, 1.68-4.18), complete response (=CR) (81.8% vs. 32.1%; odds ratio [OR], 9.56; 95% CI, 6.47-14.14), and MRD-negativity (58.4% vs.

17.1%; OR, 6.78; 95% CI, 4.53-10.15, P<0.0001; evaluable rate of 89.3% vs. 63.0%) at three-years follow-up. OS favored TECVAYLI® plus DARZALEX FASPRO® (HR, 0.46; 95% CI, 0.32-0.65; P<0.0001) across all prespecified subgroups.

At three years, OS rates were 83.3% and 65.0% for the TECVAYLI® plus DARZALEX FASPRO®arm and the control arm, respectively. In the MajesTEC-3 study, TECVAYLI® plus DARZALEX FASPRO® and SOC comparators had similar rates of Grade 3/4 (95.1% vs. 96.6%) treatment-emergent adverse events (TEAE).3 Most Grade 3/4 events were due to cytopenias and infection.3 Infections were observed with TECVAYLI® and DARZALEX FASPRO® (any grade, 96.5%; Grade 3/4, 54.1%) and DPd/DVd control (any grade 84.1%; Grade 3/4 43.4%).

Grade 3 or higher infections with TECVAYLI® and DARZALEX FASPRO® declined after the first 6 months of treatment consistent with use of established immunoglobulin supplementation and infection prophylaxis protocols, along with switch to monthly dosing. Cytokine release syndrome occurred in 60.1% of patients; all cases were Grade 1/2, did not lead to treatment discontinuation and were effectively managed using standard guidelines. Immune effector cell-associated neurotoxicity syndrome was rare and occurred in 1.1% of patients.3 Serious adverse events occurred in 70.7% of patients compared to 62.4% of patients treated with the control regimen, while treatment discontinuations due to adverse events were low (4.6% vs.

5.5%). Grade 5 TEAEs were 7.1% and 5.9% with TECVAYLI® plus DARZALEX FASPRO® and DPd/DVd control, respectively. The FDA proactively selected the teclistamab MajesTEC-3 supplemental Biologics License Application (sBLA) to participate in the Commissioner's National Priority Voucher (CNPV) Pilot Program as it aligns with the program's priority to deliver more innovative therapies for American people.

The FDA also granted the application Breakthrough Therapy Designation and Real-Time Oncology Review.