FDA Approves Janssen’s Talvey to Treat Patients with Heavily Pretreated Multiple Myeloma

Rare Daily Staff   

The U.S. Food and Drug Administration granted accelerated approval for Talvey, a first-in-class bispecific antibody for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.

The approval was granted to the Janssen Pharmaceutical Companies of Johnson & Johnson under accelerated approval based on response rate and durability of response. Continued approval for this indication is contingent upon verification and description of clinical benefit in confirmatory trial or trials.

Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells found in the bone marrow. In multiple myeloma, these plasma cells change, spread rapidly and replace normal cells in the bone marrow with tumors. In 2023, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the United States and more than 12,000 people will die from the disease, which has a five-year relative survival rate of 59.8 percent. While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels and kidney problems or infections.

Talvey is a bispecific T-cell engaging antibody that binds to the CD3 receptor on the surface of T cells and G protein-coupled receptor class GPRC5D expressed on the surface of multiple myeloma cells, non-malignant plasma cells, and healthy tissue such as epithelial cells in keratinized tissues of the skin and tongue. Talvey is approved as a weekly or biweekly subcutaneous injection after an initial step-up phase, offering physicians the flexibility to determine the optimal treatment regimen for patients.

“The clinically meaningful efficacy and safety profile observed with talquetamab in heavily pretreated patients in this clinical trial, which included patients treated with prior BCMA-targeted bispecific or CAR-T cell therapy, has been notable,” said Ajai Chari, director of Multiple Myeloma Program, professor of Clinical Medicine at the University of California, San Francisco. “Patients at this stage of disease have a poor prognosis. Talquetamab as a first-in-class therapy is a new option for patients with this difficult-to-treat blood cancer.”

The talquetamab phase 2 MonumenTAL-1 study, which included patients who had received at least four prior lines of therapy and who were not exposed to prior T-cell redirection therapy, showed meaningful overall response rates (ORR). At the biweekly dose of 0.8 mg/kg, 73.6 percent of patients achieved an ORR. With a median follow-up of nearly 6 months from first response among responders, 58 percent of patients achieved a very good partial response or better, including 33 percent of patients achieving a complete response (CR) or better. At the weekly dose of 0.4 mg/kg, 73.0 percent of patients achieved an ORR. With a median follow-up of nearly 14 (range, 0.8 to 15.4) months from first response among responders, 57 percent of patients achieved a VGPR or better, including 35 percent of patients achieving a CR or better. Responses were durable with a median duration of response not reached in the 0.8 mg/kg SC biweekly dose group and 9.5 months in the 0.4 mg/kg SC weekly dose group. Among patients receiving the 0.8 mg/kg SC biweekly dose, an estimated 85 percent of responders maintained response for at least 9 months.

The MonumenTAL-1 study also included 32 patients who were exposed to prior bispecific antibody or CAR-T cell therapy and had received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, received Talvey at the 0.4 mg/kg SC weekly dose. With a median duration of follow-up of 10.4 months, 72 percent of patients achieved an ORR per an Independent Review Committee assessment, and an estimated 59 percent of responders maintained response for at least 9 months.

The Safety Profile for Talvey includes a boxed warning for cytokine release syndrome and neurologic toxicity including immune effector cell-associated neurotoxicity syndrome. Warnings and precautions include oral toxicity and weight loss, infections, cytopenias, skin toxicity, hepatoxicity and embryo-fetal toxicity. The most common adverse reactions (≥20 percent) are pyrexia, cytokine release syndrome, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight decreased, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache. The most common Grade 3 or 4 laboratory abnormalities (≥30 percent) are lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased.

Because of the risk of CRS and neurologic toxicity, Talvey is available only through a restricted program called the Tecvali and Talvey Risk Evaluation and Mitigation Strategy (REMS).

“Although options for the treatment of multiple myeloma have expanded significantly in recent years, the disease remains incurable, and therefore, patients are in need of new treatment options,” said Michael Andreini, president and CEO, Multiple Myeloma Research Foundation. “Today’s approval of talquetamab provides patients with a new treatment approach for relapsed or refractory disease that is a welcome addition to the myeloma community.”

Photo: Michael Andreini, president and CEO, Multiple Myeloma Research Foundation