FDA Approves Janssen’s Tecvayli for the Treatment of Relapsed or Refractory Multiple Myeloma

The U.S. Food and Drug Administration granted accelerated approval to Janssen Pharmaceuticals’ Tecvayli for the treatment of adult patients with relapsed or refractory multiple myeloma, who previously received four or more prior lines of therapy, including a proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody.

Photo: Michael Andreini, President and CEO of the Multiple Myeloma Research Foundation

Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

Tecvayli (teclistamab-cqyv) is a first-in-class, bispecific T-cell engager antibody that is administered as a subcutaneous treatment. This off-the-shelf therapy is designed to activate the immune system by binding to the CD3 receptor expressed on the surface of T-cells and to the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells.

Multiple myeloma is a rare incurable blood cancer that affects a type of white blood cell called plasma cells, which are 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 2022, it is estimated that more than 34,000 people will be diagnosed with multiple myeloma, and more than 12,000 people will die from the disease in the U.S. 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, kidney problems or infections.

“Multiple myeloma is a life-threatening disease with considerable unmet need, and teclistamab is an important new treatment option for patients who have faced multiple relapses,” said Michael Andreini, President and CEO of the Multiple Myeloma Research Foundation.

Tecvayli was evaluated in MajesTEC-1, a single-arm, multi-cohort, open-label, multi-center study. The efficacy population consisted of 110 patients who had previously received at least 3 prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, and had not received prior BCMA-targeted therapy.

The main efficacy outcome measure was overall response rate (ORR) as determined by the Independent Review Committee assessment using International Myeloma Working Group 2016 criteria. ORR was 61.8 percent. With a median follow-up of 7.4 months among responders, the estimated duration of response (DOR) rate was 90.6 percent at 6 months and 66.5 percent at 9 months.

Tecvayli has a Boxed Warning for life threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS). Among patients who received Tecvayli at the recommended dose, CRS occurred in 72 percent of patients, neurologic toxicity in 57 percent, and ICANS in 6 percent. Grade 3 CRS occurred in 0.6 percent of patients and Grade 3 or 4 neurologic toxicity occurred in 2.4 percent.

Because of the risks of CRS and neurologic toxicity, including ICANS, Tecvayli is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Tecvayli REMS.

The most common adverse reactions (≥20 percent) occurring in the 165 patients in the safety population, were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20 percent) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.

Author: Rare Daily Staff