Legend Biotech’s CAR-T Carvykti Approved for R/R MM Indication in China

Legend Biotech's ciltacabtagene autoleucel (cilta-cel; marketed as Carvykti in the United States and Europe), a BCMA-directed chimeric antigen receptor T-cell (CAR-T) therapy, has been approved by China’s National Medical Products Administration (NMPA) for the treatment of adults with relapsed or refractory (r/r) multiple myeloma (MM) who previously received treatment with 3 or more lines of therapy, including 1 or more proteasome inhibitor and 1 immunomodulatory agent.¹

“The approval of cilta-cel in China market marks a key milestone and will bring significant benefits to many patients,” Ying Huang, PhD, the CEO of Legend Biotech, said in a statement.¹ “Moving forward, we will continue to pursue our goal of curing patients, expand our clinical research, and enhance the accessibility of this innovative product to benefit more patients.”

The NMPA’s decision was made with reference to results from the phase 2 CARTIFAN-1 clinical trial (NCT03758417), which took place at multiple sites in China. Out of 58 patients treated in the study who were evaluated for efficacy with a median follow-up of 37.29 months, the overall response rate was 87.9%, with 79.3% of patients having achieved a complete response (CR) or stringent CR and 86.2% of patients having achieved a very good partial response or better. Furthermore, the median duration of response was 32.56 months, the median progression-free survival was 30.13 months, and the median overall survival was not reached.

In the US, cilta-cel is approved for use in adults with relapsed and lenalidomide-refractory MM who have been treated with at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent.² This indication, for which the therapy was approved by the FDA in April 2024, is an expansion of the therapy’s previous indication in the US, which was originally restricted to adult patients with r/r MM following 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an antiCD38 monoclonal antibody, upon its initial approval by the agency in February 2022.³ The FDA’s April 2024 decision to expand the indication was informed by the results of the CARTITUDE-4 clinical trial (NCT04181827), a phase 3, randomized, open-label study evaluating cilta-cel against standard of care (SOC) therapy in patients who received 1 to 3 prior lines of therapy.⁴

“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” Binod Dhakal, MD, Associate Professor, Medical College of Wisconsin, Division of Hematology and Oncology, said in an April 2024 statement.² “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”

Later in April 2024, the FDA’s decision was followed by a decision from the European Commission (EC) to approve cilta-cel for an expanded indication in adults with r/r MM who have been treated with at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, showed disease progression on their last therapy, and have disease that is lenalidomide-refractory.⁵ The EC’s decision was likewise based on data from CARTITUDE-4. Cilta-cel was originally given conditional marketing authorization by the EC in May 2022 for adults with r/r MM who had been treated with at least 3 prior therapies, which were required to have included a proteasome inhibitor, an immunomodulatory agent, and an antiCD38 antibody, with disease progression having occurred while on the last treatment.

REFERENCES
1. Genscript subsidiary Legend Biotech achieves breakthrough with cilta-cel approval in China, offering new hope for multiple myeloma patients. News release. GenScript Biotech Corporation. August 27, 2024. Accessed August 27, 2024. https://www.genscript.com/genscript-subsidiary-legend-biotech-achieves-breakthrough.html
2. CARVYKTI® is the First and Only BCMA-Targeted Treatment Approved by the U.S. FDA for Patients with Relapsed or Refractory Multiple Myeloma Who Have Received at Least One Prior Line of Therapy. News release. Johnson & Johnson. April 6, 2024. Accessed August 27, 2024. https://www.jnj.com/media-center/press-releases/carvykti-is-the-first-and-only-bcma-targeted-treatment-approved-by-the-u-s-fda-for-patients-with-relapsed-or-refractory-multiple-myeloma-who-have-received-at-least-one-prior-line-of-therapy
3. U.S. FDA approves CARVYKTI™ (ciltacabtageneautoleucel), Janssen’s first cell therapy, a BCMA-directed CAR-T immunotherapy for the treatment of patients with relapsed or refractory multiple myeloma. News release. Janssen. February 28, 2022. Accessed August 27, 2024. https://bit.ly/35yWwjv
4. Legend Biotech announces submission of supplemental application to the U.S. FDA for expanded use of CARVYKTI® (ciltacabtageneautoleucel). News release. Legend Biotech. June 6, 2023. Accessed August 27, 2024. https://www.businesswire.com/news/home/20230606005760/en/Legend-Biotech-Announces-Submission-of-Supplemental-Application-to-the-U.S.-FDA-for-Expanded-Use-of-CARVYKTI%C2%AE-ciltacabtagene-autoleucel
5. Carvykti® (ciltacabtageneautoleucel) approved by the European commission for second-line treatment of patients with relapsed and refractory multiple myeloma. News release. Legend Biotech Corporation. April 22, 2024. Accessed August 27, 2024. https://legendbiotech.com/legend-news/carvykti-ciltacabtagene-autoleucel-approved-by-the-european-commission-for-second-line-treatment-of-patients-with-relapsed-and-refractory-multiple-myeloma/