Janssen and Legend Biotech Initiate Rolling BLA Submission to U.S. FDA for BCMA-Targeted CAR-T Therapy Ciltacabtagene Autoleucel in Relapsed/Refractory Multiple Myeloma

Today, Janssen, a Johnson & Johnson company, and Legend Biotech simultaneously announced the initiation of a rolling submission to the U.S. FDA of the Biologics License Application (BLA) for ciltacabtagene autoleucel (cilta-cel), a CAR-T therapy targeting B-cell maturation antigen (BCMA) developed in collaboration, for the treatment of adult patients with relapsed/refractory multiple myeloma.

Multiple Myeloma (MM) is an incurable blood cancer caused by the malignant transformation of white blood cells known as plasma cells. These cancerous plasma cells proliferate rapidly in the bone marrow, displacing normal cells. Although some patients with multiple myeloma are asymptomatic, most diagnosed patients present with symptoms such as fractures or pain, low red blood cell count, fatigue, hypercalcemia, renal impairment, or infections. While numerous therapies are currently available for the treatment of MM, the disease relapses in most patients after they achieve remission.

Cilta-cel is a CAR-T cell therapy with a differentiated structure, comprising a 4-1BB co-stimulatory domain and two BCMA-targeting antibody domains, which facilitates the expansion of CD8-positive T cells. BCMA is a protein highly expressed on myeloma cells. In December 2017, Janssen Biotech, Inc. and Legend Biotech entered into an exclusive global license and collaboration agreement to jointly develop and commercialize cilta-cel. This innovative CAR-T therapy was granted Breakthrough Therapy Designation by the U.S. FDA in December 2019.

▲Schematic diagram of the structure of cilta-cel (formerly known as JNJ-4528/LCAR-B38M) (Image source: Legend Biotech official website)

Latest clinical data presented at the recent American Society of Hematology (ASH) Annual Meeting demonstrated that cilta-cel continued to exhibit a very high overall response rate (ORR) in the Phase 1b/2 CARTITUDE-1 trial. With a median follow-up of 12.4 months, the ORR reached 97%, and patients experienced deepening responses over time, with 67% achieving stringent complete response. At the median follow-up of 12.4 months, the median duration of response and progression-free survival had not yet been reached.

References:

[1] Janssen Initiates Rolling Submission of a Biologics License Application to U.S. FDA for BCMA CAR-T Therapy Ciltacabtagene Autoleucel (cilta-cel) for the Treatment of Relapsed and/or Refractory Multiple Myeloma. Retrieved December 21, 2020, from https://www.janssen.com/janssen-initiates-rolling-submission-biologics-license-application-us-fda-bcma-car-t-therapy

[2] Legend Biotech Announces Initiation of Rolling Submission of Biologics License Application to U.S. FDA Seeking Approval of BCMA CAR-T Therapy Cilta-cel for the Treatment of Relapsed and/or Refractory Multiple Myeloma. Retrieved December 21, 2020, from https://www.businesswire.com/news/home/20201221005081/en

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