Johnson and Johnson approved Tecvayli plus Darzalex Faspro for 2L multiple myeloma | iPharmaCenter

Johnson & Johnson has received U.S. FDA approval for the combination of Tecvayli (teclistamab) and Darzalex Faspro (daratumumab and hyaluronidase) for adults with relapsed or refractory multiple myeloma after at least one prior line of therapy that included a proteasome inhibitor and an IMiD.

The FDA reached this decision 55 days after submission, making it the third approval granted through the Commissioner’s National Priority Voucher (CNPV) pilot program.

The regimen can now be used as early as second line and is positioned as a new option for the large proportion of patients who relapse after initial treatment.

The decision is based on the phase 3 MajesTEC-3 trial, which compared Tecvayli plus Darzalex Faspro against investigator’s choice of standard daratumumab-based regimens in patients previously treated with at least one line of therapy.

• After a median follow-up of about three years, the Tecvayli-based combination reduced the risk of disease progression or death by around 83% versus the control arm, with three-year progression-free survival of roughly 83% compared with about 30% on standard therapy.

• Overall survival also favored the experimental arm, with a hazard ratio of approximately 0.46 and three-year overall survival rates of 83.3% versus 65.0%.

• Response endpoints showed the depth of benefit with the bispecific–anti‑CD38 doublet. Overall response rate reached close to 90% in the Tecvayli plus Darzalex Faspro group versus about 75% with control regimens, and complete response or better was reported in more than 80% of patients compared with roughly one‑third in the comparator arm.

• Rates of MRD negativity were also higher with the combination, exceeding 50% at three years versus below 20% in the control group.

These data collectively indicate deeper and more sustained disease control than current daratumumab-based standards in this setting.

The safety profile reflected expected class effects for T‑cell–redirecting and anti‑CD38 therapy. Grade 3–4 treatment-emergent adverse events occurred in more than 95% of patients in both arms, driven mainly by cytopenias and infections.

Tecvayli is a subcutaneous bispecific antibody that links CD3-positive T cells to BCMA-expressing myeloma cells, thereby redirecting T cells to kill malignant plasma cells. Darzalex Faspro is a subcutaneous formulation of daratumumab combined with hyaluronidase, targeting CD38 on myeloma cells and selected immune cells and already approved across multiple lines of therapy in multiple myeloma. The MajesTEC‑3 results support the use of this fully subcutaneous doublet as a fixed, off‑the‑shelf regimen earlier in the treatment course, rather than reserving bispecific therapy only for heavily pretreated disease.

Regulators prioritised review of the MajesTEC‑3 supplemental application, including via the FDA’s Real‑Time Oncology Review process and Breakthrough Therapy Designation. With this approval, Johnson & Johnson moves to consolidate Tecvayli as a backbone component within its myeloma portfolio, and further studies are ongoing to test the drug in additional combinations and earlier disease settings as part of the broader MajesTEC clinical programme.