Janssen/Legend Biotech's BCMA CAR-T Therapy Cilta-cel Receives FDA Priority Review for Relapsed/Refractory Multiple Myeloma

May 28, 2021 /BioonBIOON/ -- Nanjing Legend Biotech (Legend Biotech) recently announced that the U.S. Food and Drug Administration (FDA) has accepted the BCMA CAR-T cell therapy ciltacabtagene autoleucel (cilta-cel, formerly known as JNJ-4528/LCAR-B38M,LCAR-B38M CAR-T Cell Autologous Infusion Preparation） Biologics License Application (BLA) and granted priority review. The drug is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM). The FDA has set the Prescription Drug User Fee Act (PDUFA) target date as November 29, 2021. In December 2019,FDACilta-cel was granted Breakthrough Therapy Designation (BTD). In April this year, the Marketing Authorization Application (MAA) for cilta-cel was submitted to the European Medicines Agency (EMA), which had previously granted it Accelerated Assessment status.

Dr. Ying Huang, Chief Executive Officer and Chief Financial Officer of Legend Biotech, stated: “Based on the research data reported to date, cilta-cel has shown significant promise in patients with multiple myeloma who have previously received multiple therapies. Today’s priority review marks another milestone for cilta-cel. We look forward to continuing our collaboration with Janssen, and”FDAcollaboration, to bring this transformative therapy to patients in need of new treatment options.”

cilta-cel is an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy., for the treatment of relapsed or refractory multiple myeloma (RRMM). Cilta-cel is an autologous CAR-T therapy in which the patient's own T cells are reprogrammed to target and eradicate cancer.

cilta-cel is a unique, structurally distinct CAR-T cell therapy comprising a 4-1BB co-stimulatory domain and two BCMA-targeting single-domain antibodies, characterized by preferential expansion of CD8+ T cells. CAR-T cells are a type of cell therapy that utilize the patient's`Autoimmunity`An innovative approach that harnesses the power of the system to eliminate cancer cells. BCMA is a protein highly expressed on myeloma cells.

cilta-cel was designed and developed by Legend Biotech, a subsidiary of GenScript. In December 2017, Janssen Biotech, Inc., a Johnson & Johnson company, entered into an exclusive global license and collaboration agreement with Legend Biotech to develop and commercialize cilta-cel. In the United States,FDAcilta-cel was granted Breakthrough Therapy designation in December 2019 and Orphan Drug designation in February 2019. In the European Union, the European Commission (EC) granted Orphan Drug designation to cilta-cel in February 2020 and Priority Medicines (PRIME) designation in April 2019.In China, the National Medical Products Administration (NMPA) granted cilta-cel Breakthrough Therapy Designation (BTD) in August 2020.

Structural Features of cilta-cel

The BLA and MAA for cilta-cel are both based on data from the Phase Ib/II CARTITUDE-1 study (NCT03548207). This is an ongoing Phase Ib/II, open-label, multicenter study evaluating the efficacy and safety of cilta-cel in adult patients with relapsed or refractory multiple myeloma (RRMM). The study enrolled 97 patients who had received a median of 6 prior lines of therapy (range: 3–18); 88% (n=85) were triple-refractory, 42% (n=41) were penta-refractory, and 99% (n=96) were refractory to their most recent therapy. In this study, cilta-cel was successfully manufactured for all patients. The primary objective of the Phase Ib portion was to assess the safety and determine the dose of cilta-cel. The Phase II portion will evaluate the efficacy of cilta-cel, with the primary endpoint being the overall response rate (ORR).

The latest data presented at the 62nd ASH Annual Meeting in early December 2020 showed: deepening of response over time, with a median follow-up of 12.4 months (range: 1.5–24.9), as determined by Independent Review Committee (IRC) assessment,97% of patients achieved a response (ORR=97%), including:67% of patients achieved a stringent complete response (sCR=67%)、26% of patients achieved a very good partial response (VGPR=26%), and 4% achieved a partial response (PR=4%). At a median follow-up of 12.4 months, median progression-free survival (PFS) was not reached, with a 12-month PFS rate of 77% (95% CI: 66–84) and a 12-month overall survival rate of 89% (95% CI: 80–94). Regarding safety, the incidence of grade ≥3 cytokine release syndrome (CRS) was 5%, and the incidence of grade ≥3 neurotoxicity was 10%.

The latest long-term follow-up data from this study will be presented at the 2021 ASCO Annual Meeting held in early June. (Bioon.com)

Original Source: U.S. Food and Drug Administration Grants BCMA CAR-T Cilta-cel Priority Review for the Treatment for Relapsed/Refractory Multiple Myeloma