The FDA issued a CRL for the therapy, to be marketed as Ryoncil, in August 2023.
Mesoblast is continuing its push to try and get its mesenchymal stromal cell therapy remestemcel-L approved to treat pediatric and adult steroid-refractory acute graft versus host disease (SR-aGVHD) under the name Ryoncil, with plans including conducting an additional single-arm trial informed by a recent Type A meeting with the FDA.1
"We had a very productive meeting with the FDA’s review team, allowing us to establish the path forward for potential approval of remestemcel-L in SR-aGVHD. We are gathering the additional potency assay data required to demonstrate the ability of Mesoblast’s potency assay to show both the product used in the Phase 3 trial in children and the product made for commercial release are standardized,” Silviu Itescu, MBBS, chief executive officer, Mesoblast, said in a statement.1 “ In parallel, we are focused on initiating a registration trial in adults in partnership with world-leading investigators at the Blood and Marrow Clinical Trials Network.”
Mesoblast met with the FDA after receiving a complete response letter (CRL) from the agency after reviewing remestemcel-L's biologics license application (BLA) in August.2 This marked the second CRL Mesoblast had received for the therapy after originally submitting a BLA in 2020.3
During the Type A meeting, Mesoblast summarized the body of data to the FDA, including data supporting consistently high survival in children with SR-aGVHD who received remestemcel-L treatment.1 The FDA reiterated that the key issue Mesoblast must address is consistent efficacy of commercial product, and that the company must provide further evidence from potency assays – the potency assay used in the Phase 3 trial MSB-GVHD001 (NCT02336230) was not considered a suitable assay. Mesoblast intends to generate new potency assay data from the trial in the coming months, which it believes will provide a suitable link between product used for the pediatric indication to the adult indication.
Mesoblast believes these additional data will provide a link between the RYONCIL product that was used in the Phase 3 trial MSB-GVHD001 for the pediatric indication to the RYONCIL product which will be used in a future trial for the adult indication. For the adult indication, Mesoblast plans to initiate a single-arm registration trial design in adults and children over age 12 with SR-aGVHD who have failed both steroids and a second line agent, such as ruxolitinib, with external controls, to meet the FDA’s concerns. The trial will be performed in partnership with the Blood and Marrow Clinical Trials Network. The FDA indicated that it was willing to consider this proposed registrational trial design in adults, pending agreement on the suitability of the potency assay.