China-based Legend Biotech Corporation (NASDAQ: LEGN) has announced that Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved Carvykti (ciltacabtagene autoleucel), a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of adults with relapsed or refractory multiple myeloma. The approval is limited to patients who have not previously received CAR-T cell infusion therapy targeting BCMA and who have received three or more lines of therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody, with disease relapse or non-response to the most recent therapy.
Carvykti: Mechanism and Development
Carvykti is a BCMA-directed, genetically modified autologous T-cell immunotherapy that reprograms a patient’s own T-cells with a transgene encoding a chimeric antigen receptor (CAR) targeting BCMA. BCMA is primarily expressed on malignant multiple myeloma B-lineage cells, late-stage B-cells, and plasma cells. The Carvykti CAR protein features two BCMA-targeting single-domain antibodies designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.
Global Approvals and Partnerships
Carvykti was approved by the US Food and Drug Administration in February 2022 and granted conditional marketing authorization by the European Commission in May 2022. The drug is being co-developed globally by Legend Biotech in partnership with Janssen under a December 2017 deal.
Clinical Trial Results
The approval is based on data from the pivotal Phase Ib/II CARTITUDE-1 study, which included patients who received a median of six prior treatment regimens. In the study, a one-time treatment with ciltacabtagene autoleucel resulted in durable responses, with 96.9% (95% CI, 91.2-99.4) of patients with relapsed or refractory multiple myeloma (RRMM) in the non-Japanese population responding to therapy (n=97). A total of 67% (95% CI, 56.7-76.2) achieved a stringent complete response (sCR), with no signs or symptoms of disease observed post-treatment. The efficacy results in Japanese patients were consistent with the non-Japanese population. At a median of 18 months follow-up, the median duration of response (DOR) was 21.8 months in non-Japanese patients.
Safety Profile
The safety of cilta-cel was evaluated in 106 adult patients in the CARTITUDE-1 study, including 97 non-Japanese and 9 Japanese participants. Adverse reactions were observed in 105 (99.1%) of 106 patients treated with cilta-cel. The most common adverse reactions included cytokine release syndrome (94.3%), cytopenia (79.2%), neutropenia (75.5%), thrombocytopenia (59.4%), anemia (51.9%), neurologic events (39.6%), infections (19.8%), and hypogammaglobulinemia (11.3%).-Fineline Info & Tech
