Johnson & Johnson's First-in-Class GPRC5D/CD3 Bispecific Antibody TALVEY™ (Talquetamab) Receives FDA Accelerated Approval for Relapsed/Refractory Multiple Myeloma

On August 10, Johnson & Johnson announced that the U.S. FDA granted accelerated approval for the company's GPRC5D/CD3 bispecific antibody TALVEY™ (talquetamab) for marketing. It is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have previously received at least four prior lines of therapy, including proteasome inhibitors, immunomodulatory agents, and CD38 antibodies.

Talquetamab is a first-in-class, off-the-shelf bispecific T-cell engager antibody that simultaneously targets GPRC5D on MM cells and CD3 on T cells. GPRC5D, known as a G protein-coupled orphan receptor, is a novel drug target that is overexpressed on malignant plasma cells and its expression in normal tissues is limited to the skin (hair follicles and eccrine sweat glands) and testes (seminiferous tubules), with its expression level being relatively independent of the target BCMA. Talquetamab activates CD3-positive T cells, inducing T-cell-mediated killing of GPRC5D-positive MM cells.

TALVEY™ Approved for Weekly or Biweekly Subcutaneous (SC) Injection After Initial Intensification Phase, Offering Flexibility for Physicians to Determine the Optimal Treatment Regimen for Patients.

This approval is based on the results of the Phase II MonumenTAL-1 study, which aimed to evaluate the efficacy of subcutaneous talquetamab in patients with R/R MM, including those who had received at least four prior lines of therapy and had not been treated with T-cell therapy (n=187). The study demonstrated a meaningful overall response rate (ORR). When administered every two weeks at a dose of 0.8 mg/kg subcutaneously, 73.6% of patients (95% Confidence Interval [CI], range 63.0–82.4) achieved ORR. With a median follow-up time of nearly 6 months from the first response (range 0–9.5 months), 58% of patients achieved a very good partial response (VGPR) or better, with 33% achieving a complete response (CR) or better.

When the dosing frequency was 0.4 mg/kg administered subcutaneously once weekly, 73.0% of patients (95% CI, range 63.2–81.4) achieved ORR. The median follow-up time from the first response was approximately 14 months (range 0.8 to 15.4 months), with 57% of patients achieving VGPR or better, including 35% who reached CR or better.

The median duration of response was not reached in the 0.8 mg/kg (once every two weeks, SC) dose group, and was 9.5 months in the 0.4 mg/kg (once weekly, SC) dose group. It was estimated that 85% of subjects in the 0.8 mg/kg (once every two weeks, SC) dose group had a response lasting at least 9 months.

Talquetamab was granted Breakthrough Therapy Designation by the U.S. FDA in June 2022 for the treatment of adult patients with R/R MM who have previously received at least four prior lines of therapy, including proteasome inhibitors, immunomodulatory agents, and anti-CD38 antibodies. In May 2021 and August 2021, talquetamab was designated as an orphan drug for the treatment of multiple myeloma by the U.S. FDA and the European Commission, respectively. In January 2021, talquetamab received PRIME designation from the European Commission.

Multiple Myeloma is a key focus area for Johnson & Johnson. In the future, through strategies combining mono/bispecific antibodies, cell therapies, and induced pluripotent stem cells, Johnson & Johnson aims to redefine the treatment paradigm for MM.

Bortezomib (Velcade) is the first-generation product developed by Johnson & Johnson, while Daratumumab (Darzalex) is the first biologic drug launched in this field, expanding its use from fourth-line treatment and above to current first-line treatment. Carvykti (BCMA CAR-T), jointly developed by Johnson & Johnson and Legend Biotech, is another key product in their pipeline. The first-in-class BCMAxCD3 bispecific antibody Teclistamab has also been approved by the FDA for marketing. Talquetamab is expected to be another promising product in the multiple myeloma (MM) field.

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