▎WuXiEdited by Kant Content Team

Johnson & Johnson announced today,The US FDA Oncologic Drugs Advisory Committee (ODAC) unanimously voted (11 to 0) to recommend the CAR-T therapy Carvykti (ciltacabtagene autoleucel, cilta-cel), jointly developed by Johnson & Johnson and Legend Biotech, for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM).These patients had previously received at least one prior line of therapy, including proteasome inhibitors (PI) and immunomodulatory drugs (IMiD), and were refractory to lenalidomide.The supplemental Biologics License Application (sBLA) for Carvykti to treat this patient population is currently under FDA review, with a PDUFA target date of April 5, 2024.

This committee reviewed the survival and safety data from the CARTITUDE-4 Phase 3 clinical study,And unanimously agreed that the risk-benefit assessment of Carvykti for RRMM patients is favorable.This application is based on the CARTITUDE-4 study data, an international, randomized, open-label Phase 3 study designed to evaluateCarvyktiCompare the efficacy and safety of standard-of-care (SOC) regimens in adult patients with lenalidomide-refractory RRMM who have received 1-3 prior lines of therapy. The SOC regimens in the study include pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd).

According to the documents related to the ODAC meeting published by the FDA, based on the assessment of the Independent Review Committee (IRC),In the CARTITUDE-4 trial, treatment with Carvykti demonstrated a statistically significant improvement in progression-free survival (PFS) compared to the standard therapy group (HR=0.41, 95% CI: 0.30-0.56, p<0.0001).

▲FDA'sPFS Analysis Results of the CARTITUDE-4 Trial (Image Source: Reference [2])

At the time of the second interim analysis, the median overall survival (OS) had not yet been reached in the Carvykti group, while the estimated median OS in the standard treatment group was 26.7 months (HR=0.78, 95% CI: 0.51-1.20).

▲FDA'sOS Analysis Results of the CARTITUDE-4 Trial (Image Source: Reference [2])

According to the industry media Fierce Biotech, the main reason for FDA convening the advisory committee this time is to discuss the relatively unfavorable PFS shown by the Carvykti group of patients in the first few months during the trial period. Johnson & Johnson pointed out in the meeting that the unfavorable early PFS results were mainly due to the poor bridging treatment conducted before the patients received the CAR-T therapy, rather than an issue with the Carvykti therapy itself.During the meeting, ODAC experts believed that the long-term benefits demonstrated by the Carvykti therapy in these patients should not be overturned by initially non-statistically significant results.

It is worth mentioning that,The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has also recently recommended Carvykti for the treatment of the same patient population with RRMM based on data from the CARTITUDE-4 trial.

Carvykti is a CAR-T therapy targeting B-cell maturation antigen (BCMA)., which expresses a chimeric antigen receptor containing a 4-1BB co-stimulatory domain and two antibody domains targeting BCMA. It was approved by the FDA for marketing in February 2022 and received conditional marketing approval from the EU in May for the treatment of RRMM patients who have received at least four prior lines of therapy. In December 2017, Legend Biotech entered into an exclusive global license and collaboration agreement with Janssen to jointly develop and commercialize Carvykti.

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References:

[1] U.S. FDA Oncologic Drugs Advisory Committee recommends CARVYKTI® (ciltacabtagene autoleucel) for the earlier treatment of patients with relapsed or refractory multiple myeloma. Retrieved March 15, 2024 from https://www.prnewswire.com/news-releases/us-fda-oncologic-drugs-advisory-committee-recommends-carvykti-ciltacabtagene-autoleucel-for-the-earlier-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma-302090580.html

[2] FDA Briefing Document. Retrieved March 15, 2024 https://www.fda.gov/media/176986/download

[3] Despite early death concerns, FDA advisers back J&J and Legend's Carvykti for earlier myeloma. Retrieved March 15, 2024 from https://www.fiercepharma.com/pharma/fda-advisers-back-carvykti-earlier-multiple-myeloma-treatment-despite-early-death-concerns

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