FDA Carvykti(Ciltacabtagene Autoleucel), Legend Biotech’s CAR-T Therapy, Advancing from Fourth-Line to Second-Line Treatment for Multiple Myeloma
FDA Carvykti(Ciltacabtagene Autoleucel), Legend Biotech’s CAR-T Therapy, Advancing from Fourth-Line to Second-Line Treatment for Multiple Myeloma
The long-awaited moment has finally arrived, and the lingering anxiety can now be put to rest.
CARVYKTI has successfully advanced to second-line treatment for multiple myeloma.
According to a press release from Legend Biotech, CARVYKTI is the first approved BCMA-targeted therapy for second-line treatment of MM, including CAR-T cell therapy, bispecific antibodies, and antibody-drug conjugates (ADCs).
Success in Second-Line Treatment Approval
On April 5, 2024 (local time), Legend Biotech announced that the U.S. FDA has approved BCMA CAR-T cell therapy CARVYKTI for the treatment of relapsed or refractory multiple myeloma (RR MM) patients who have previously received at least one prior line of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), and are refractory to Lenalidomide.
This approval of CARVYKTI is based on the positive results of the CARTITUDE-4 study. The study showed that compared to two standard treatment regimens, Pomalidomide, Bortezomib, and Dexamethasone (PVd) or Daratumumab, Pomalidomide, and Dexamethasone (DPd), CARVYKTI significantly improved progression-free survival (PFS) in adult patients with relapsed and Lenalidomide-refractory multiple myeloma who had previously received one to three lines of therapy. This result has statistical and clinical significance.
The Nerve-wracking Process
In fact, it took CARVYKTI only about two years to leap from fourth-line or later treatment for multiple myeloma to second-line treatment, but the process was nerve-wracking.
In February 2022, CARVYKTI was first approved by the FDA for the treatment of multiple myeloma in the fourth-line or later setting. Subsequently, within the same year, it received marketing approvals from the European Union and Japan. Legend Biotech also submitted a marketing application for Ciltacabtagene Autoleucel (CARVYKTI) to the National Medical Products Administration (NMPA) in China by the end of 2022 and received acceptance.
Time progressed to the busy year of 2023.
In January 2023, Legend Biotech unblinded the Phase 3 CARTITUDE-4 study of CARVYKTI and announced that the study had met its primary endpoint. At the same time, the company planned to communicate with health authorities, foreshadowing CARVYKTI’s official push into the frontline treatment of multiple myeloma.
In May 2023, Legend Biotech’s partner Johnson & Johnson submitted a Type II variation application to the European Medicines Agency (EMA) with data from the CARTITUDE-4 study to expand the indication of CARVYKTI.
In June 2023, Legend Biotech submitted a supplemental Biologics License Application (sBLA) to the U.S. FDA to expand the indication of CARVYKTI to include adult patients with relapsed and Lenalidomide-refractory multiple myeloma who have previously received at least one line of therapy (including a proteasome inhibitor and an immunomodulatory agent). The PDUFA date was set for April 5, 2024.
Before the PDUFA date for CARVYKTI, two events occurred that added a touch of uncertainty about whether CARVYKTI would be approved smoothly.
➤ In November 2023, the FDA postponed its decision on BMS/2seventy bio’s application for the BCMA CAR-T therapy Abecma for second-line treatment of multiple myeloma and planned to convene an Oncologic Drugs Advisory Committee (ODAC) meeting to discuss the approval. (As of the publication of this article, the application has been approved.)
➤ In January 2024, a document filed by Legend Biotech with the U.S. Securities and Exchange Commission (SEC) showed that the U.S. FDA would convene its Oncologic Drugs Advisory Committee (ODAC) to discuss the supplemental Biologics License Application for CARVYKTI for the treatment of multiple myeloma in patients who have previously received at least one line of therapy.
The clouds cleared when, in March 2024, the FDA’s Oncologic Drugs Advisory Committee unanimously voted 11:0 that the risks of CARVYKTI did not outweigh the benefits of treatment – particularly the improvement in progression-free survival (PFS) recorded in the CARTITUDE-4 trial.
On the PDUFA date of April 5, 2024, CARVYKTI was successfully approved, marking the end of this process.
In Summary
Since CARVYKTI began its international market expansion, Legend Biotech has been busy for several years, but the results have been gratifying. With the expansion of the indication, more patients will be able to receive CARVYKTI treatment. This means increased production pressure on Legend Biotech and Johnson & Johnson.