FDA Approves Remestemcel-L in Pediatric Patients With Acute GVHD

• The FDA has approved remestemcel-L (Ryoncil) for the treatment of pediatric patients with steroid-refractory acute graft-vs-host disease (SR-aGVHD).
• Remestemcel-L is the first agent for patients with SR-aGVHD under the age of 12.
• The application of remestemcel-L is supported by data from the phase 3 GVHD001/002 clinical trial (NCT02336230).

Remestemcel-L is now an FDA-approved treatment for pediatric patients with SR-aGVHD, making it the first agent for this patient population.¹

The approval was supported by data from the phase 3 GVHD001/002 clinical trial. Fifty-four pediatric patients with SR-aGVHD were evaluated across 20 centers in the US, and 89% of patients had grade C/D disease.²

The trial met its primary end point of day 28 overall response (OR) with 70.4% vs 45% (P =.0003). The day 28 OR was considered highly predictive of improved survival through day 100, with 87% vs 47% patients who did not reach day 28 OR (P =.0001).

A matched control group of pediatric patients from the Mount Sinai Acute GVHD International Consortium (MAGIC) given best available therapy was also used for comparison. Remestemcel-L led to a higher day 28 OR, with 70% vs 43%, and higher day 100 survival, with 74% vs 57%. Using matched propensity scoring, 67% of patients with high-risk disease receiving remestemcel-L achieved a day 28 OR and were alive after 180 days vs 10% of patients in the MAGIC group who received best available therapy.

A 4-year survival study conducted by the Center for International Blood and Marrow Transplant Research also found that survival benefits of remestemcel-L were durable, with 67% survival at 6 months, 63% at 1 year, 51% at 2 years, and 49% at 4 years. With best available therapy, patients had an expected 2-year survival of 25% to 38%.

A complete response letter (CRL) was issued to the biologics license application (BLA) in August 2023. The CRL noted that there was insufficient data to support approval. The FDA also required Mesoblast, the sponsor of remestemcel-L, to address ongoing problems regarding chemistry, manufacturing, and controls (CMC) before resubmitting the BLA.^2,3

Mesoblast announced a controlled study in high-risk adults to meet the FDA requirements, and in March 2024, the FDA decided that there was sufficient evidence to resubmit the BLA. Mesoblast resubmitted the BLA on July 8, 2024. The new filing also addressed the remaining CMC issues.³

REFERENCES:

1. FDA approves remestemcel-L-rknd for steroid-refractory acute graft versus host disease in pediatric patients. News release. FDA. December 18, 2024. Accessed December 18, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-remestemcel-l-rknd-steroid-refractory-acute-graft-versus-host-disease-pediatric

2. Mesoblast resubmits biologics license application (BLA) with United States Food & Drug Administration (FDA) for approval of Ryoncil® in children with steroid-refractory acute graft-versus-host disease (SR-aGVHD). News release. Mesoblast Limited. July 9, 2024. Accessed October 17, 2024. https://tinyurl.com/2s38v4ab

3. FDA accepts Mesoblast’s biologics license application (BLA) for Ryoncil® in children with steroid-refractory acute graft-versus-host disease (SR-aGVHD). News release. Mesoblast Limited. July 23, 2024. Accessed October 17, 2024. https://tinyurl.com/2wj9kcrz