BLA for steroid-refractory acute graft versus host disease candidate to be resubmitted

BLA for steroid-refractory acute graft versus host disease candidate to be resubmitted | Image Credit: © Araki Illustrations - © Araki Illustrations - stock.adobe.com.

After a Complete Response Letter (CRL) for remestemcel-L (Ryoncil), Mesoblast Limited's lead product candidate to treat steroid-refractory acute graft versus host disease (SR-aGVHD), was issued on August 4, 2023, the company expects to resubmit a Biologics License Application this quarter.^1,2

According to press release from Mesoblast that highlighted a corporate presentation at a recent investor conference, Silviu Itescu, Mesoblast's chief executive, made the announcement, noting potential FDA approval in the second half of the 2024 calendar year.¹

The CRL issued in August 2023 came with a request for more data to support marketing approval. At the time of CRL issuance, the FDA completed the Pre-License Inspection and did not issue any Form 483. No objectionable conditions were found, and the federal agency “acknowledged in the resubmission review that changes implemented appear to improve assay performance relative to the original version of the assay used in the pediatric phase 3 trial,” according to the press release.^2,3

In a single-arm, phase 3 trial that enrolled 54 children with SR-aGVHD, a pre-specified primary outcome was met. In August 2020, the Oncologic Drugs Advisory Committee voted 9 to 1 in favor of remestemcel-L’s pediatric population efficacy. In September of the same year, the FDA noted that additional steps were needed for approval. The January 2023 BLA resubmission for remestemcel-L included long-term follow-up data from the Center for International Blood and Marrow Transplant Research phase 3 trial.²

Fifty-percent survival through 4 or more years during follow up in remestemcel-L-treated patients was observed in the phase 3 trial. According to Mesoblast, less than 20% survival was expected based on severity of disease. A post-hoc propensity matched study was also included in the resubmission, demonstrating that 6-month survival was 67% with remestemcel-L compared to 10% with other nonapproved therapies.²

These results were demonstrated in highest-risk patients (identified using Mount Sinai Acute GVHD International Consortium). These data further support remestemcel-L use for the proposed study to treat high-risk adults with SR-aGVHD, stated Mesoblast.²

References:

1. Mesoblast corporate presentation at investor conference. Mesoblast Limited. Press release. June 3, 2024. Accessed June 4, 2024. https://investorsmedia.mesoblast.com/static-files/401875e0-ce8e-4bc5-8c44-fc87a5b09702
2. Fitch, J. FDA issues complete response letter to remestemcel-L for graft-versus-host disease treatment. Contemporary Pediatrics. August 10, 2024. Accessed June 4, 2024. https://www.contemporarypediatrics.com/view/fda-issues-complete-response-letter-to-remestemcel-l-for-graft-versus-host-disease-treatment
3. Mesoblast receives Complete Response from US Food and Drug Administration for Biologics License Application for steroid-refractory acute graft versus host disease in children. August 4, 2024. Accessed June 4, 2024. https://investorsmedia.mesoblast.com/static-files/422cd6da-a0b9-49cf-a177-7fd106f111f2