FDA Accepts Mesoblast's Biologics License Application for Ryoncil in Pediatric SR-aGVHD

FDA Accepts BLA Resubmission

Mesoblast Limited, a global leader in allogeneic cellular medicines, has announced that the United States Food and Drug Administration (FDA) has accepted its Biologics License Application (BLA) resubmission for Ryoncil (remestemcel-L). The BLA is for the treatment of children with steroid-refractory acute graft versus host disease (SR-aGVHD). The FDA considers the resubmission to be a complete response, and Mesoblast anticipates a decision on or before January 7, 2025.

The resubmission, made on July 8, 2024, addressed remaining Chemistry, Manufacturing, and Control (CMC) items. This followed an FDA communication in March 2024 indicating that the available clinical data from the Phase 3 study MSB-GVHD001 appeared sufficient to support the BLA submission. Additionally, a Pre-License Inspection (PLI) of the manufacturing process conducted in May 2023 did not result in any Form 483 issues.

About Ryoncil

Ryoncil (remestemcel-L) is an investigational therapy comprising culture-expanded mesenchymal stromal cells derived from the bone marrow of an unrelated donor. It is administered to patients via intravenous infusions. Ryoncil has immunomodulatory properties that counteract the inflammatory processes implicated in SR-aGVHD by inhibiting the activation and proliferation of effector T cells, down-regulating pro-inflammatory cytokines, and recruiting anti-inflammatory cells to affected tissues.

The FDA granted remestemcel-L Fast Track and Priority Review designations, facilitating the development and expedited review of therapies for serious conditions that fill unmet medical needs.

Phase 3 Trial Results

The Phase 3 Study GVHD001/002 was conducted in 54 children across 20 centers in the US, where Ryoncil was used as the first line of treatment for those who failed to respond to steroids for acute GVHD. The trial met its primary endpoint, achieving a 70.4% overall response rate at Day 28 compared to 45% in the control group (p=0.0003). This response was highly predictive of improved survival through Day 100 (87% vs. 47%, p=0.0001).

Compared to a matched control group from the Mount Sinai Acute GVHD International Consortium (MAGIC) database, Ryoncil treatment resulted in higher Day 28 overall response rates (70% vs. 43%) and higher Day 100 survival rates (74% vs. 57%). A propensity-matched study further demonstrated that 67% of high-risk children treated with Ryoncil were alive after 180 days, compared to just 10% in the MAGIC group.

About SR-aGVHD

Acute GVHD occurs in approximately 50% of patients who receive an allogeneic bone marrow transplant, with over 30,000 such transplants performed annually worldwide. SR-aGVHD is associated with mortality rates as high as 90% and significant hospital stay costs. Currently, there are no FDA-approved treatments for children under 12 with SR-aGVHD, highlighting the urgent need for effective therapies.

Survival outcomes for severe SR-aGVHD have not improved over the past two decades, underscoring the critical need for new treatment options.