The resubmission, which included new long-term follow-up data and a post-hoc propensity match study, was issued a complete response letter by the federal agency, which requires “more data to support marketing approval,” according to a press release from Mesoblast Limited.
The FDA recently issued a complete response letter (CRL) to Mesoblast Limited for its pediatric steroid-refractory acute graft versus host disease (SR-aGVHD) treatment candidate, remestemcel-L, noting that more data is needed to support the marketing approval.
The CRL follows a Biologics License Application (BLA) resubmission to the FDA from Mesoblast. According to the company, 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.
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.
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. 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.
To meet the new data requirements presented in the complete response, Mesoblast is set to conduct a targeted, controlled study in “the highest-risk adults with the greatest mortality.” The company states this study will be in line with its overall commercial strategy; a sequenced progression from pediatric to adult SR-aGVHD indications. The company expects to include adult patients with the highest SR-aGVHD risk where existing therapy has not improved outcomes and 90-day survival “remains as low as” 20% to 30%.
Mesoblast receives Complete Response from US Food and Drug Administration for Biologics License Application for steroid-refractory acute graft versus host disease in children. Mesoblast Limited. Press release. August 4, 2023. Accessed August 10, 2023. https://investorsmedia.mesoblast.com/static-files/422cd6da-a0b9-49cf-a177-7fd106f111f2