The Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for remestemcel-L (RyoncilTM; Mesoblast Limited) for the treatment of children with steroid-refractory acute graft versus host disease (SR-aGVHD).
Remestemcel-L consists of culture-expanded mesenchymal stem cells derived from the bone marrow of an unrelated donor. It is believed to work by down-regulating the production of proinflammatory cytokines, increasing production of anti-inflammatory cytokines, and enabling recruitment of naturally occurring anti-inflammatory cells to involved tissues.
The BLA is supported by data from 3 clinical trials that included 309 children with SR-aGVHD. Results across all trials showed consistent treatment responses and survival outcomes with 66% of patients (n=204) achieving an overall response at Day 28 after a 4-week course of remestemcel-L administered by intravenous infusion. Moreover, among International Bone Marrow Transplant Registry Severity Index grade C/D patients, which accounted for 82% of all treated patients, the Day 28 overall response was 65%. Day 28 responders also had greater survival rates vs nonresponders (84% vs 39% at Day 100, and 83% vs 38% at Day 180). Remestemcel-L was well tolerated with no infusion-related toxicity and no identified safety concerns.
Additionally, data from an open-label phase 3 trial evaluating remestemcel-L in 55 children with SR-aGVHD (89% of whom had grade C/D disease) support the application. Findings from the trial showed that 70% of patients treated with remestemcel-L achieved an overall response at Day 28 and 75% achieved Day 100 survival. These outcomes were superior to those from a cohort of 30 pediatric patients with SR-aGVHD from the Mount Sinai Acute GVHD International Consortium (Day 28 overall response was 43% and Day 100 survival was 57%).
Remestemcel-L is also being investigated as a treatment for patients with acute respiratory distress syndrome caused by COVID-19, among other rare diseases.
A Prescription Drug User Fee Act (PDUFA) target date of September 30, 2020 has been set for this application. If approved, the Company expects to launch Ryoncil in 2020.
For more information visit mesoblast.com.