FDA Accepts Remestemcel-L BLA Resubmission for Acute GVHD

Microscopic image of bone marrow cells - Generated with Google Gemini AI

• The FDA has accepted the resubmitted biologics license application (BLA) of remestemcel-L (Ryoncil) for the treatment of pediatric patients with steroid-refractory acute graft-vs-host disease (SR-aGVHD).
• If approved, remestemcel-L would be the first agent for patients with SR-aGVHD under the age of 12.
• A Prescription Drug User Fee Act (PDUFA) target action date of January 7, 2025, has been set.

The FDA has accepted the resubmitted BLA for remestemcel-L for pediatric patients with SR-aGVHD, following a complete response letter (CRL) issued in August 2023. ¹

A PDUFA target action date of January 7, 2025, has been set. If the FDA approves the BLA, remestemcel-L would become the first agent for pediatric patients under 12 with SR-aGVHD.

“We have worked closely with the agency and thank them for their ongoing guidance, facilitating the potential approval of [remestemcel-L] and addressing the urgent need for a therapy that improves the dismal survival outcome in children with SR-aGVHD,” said Silviu Itescu, MBBS, FRACP, chief executive officer of Mesoblast, in a press release.²

The CRL noted that there was insufficient data to support approval. The FDA also required Mesoblast, remestemcel-L’s manufacturer, to address ongoing problems regarding chemistry, manufacturing, and controls (CMC) before resubmitting the BLA.³

The company 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 addresses the remaining CMC issues.²

Remestemcel-L was granted a fast track designation from the FDA, which is intended to expedite the development and review of agents that treat serious conditions and fill unmet needs, as well as a priority review designation that is given to drugs that provide significant improvements to safety or efficacy over existing treatments.¹

About the Phase 3 GVHD001/002 Trial

The application of remestemcel-L is supported by data from the phase 3 GVHD001/002 clinical trial (NCT02336230). 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% in 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) treated with the best available therapy was also used for comparison. Here, remestemcel-L led to a higher day 28 OR, with 70% vs 43%, and higher day 100 survival, with 74% vs 57%. Further, using matched propensity scoring, 67% of high-risk patients 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. Comparatively, these patients had an expected 2-year survival of 25% to 38% with best available therapy.

REFERENCES:

1. 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 July 23, 2024. https://tinyurl.com/2wj9kcrz

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 July 23, 2024. https://tinyurl.com/2s38v4ab

3. Mesoblast receives complete response from U.S. Food and Drug Administration for biologics license application for steroid-refractory acute graft versus host disease in children. News release. Mesoblast Limited. August 3, 2023. Accessed July 23, 2024. https://tinyurl.com/4mpt4yc5