FDA Accepts Mesoblast’s BLA for Remestemcel-L for Steroid-Refractory GvHD
After 3 tries, Mesoblast finally has a PDUFA date for its MSC therapy.
Silviu Itescu, MBBS, FRACP
The FDA has accepted Mesoblast’s biologics license application (BLA) for remestemcel-L mesenchymal stromal cell therapy, to be marketed as Ryoncil, for the potential treatment of steroid refractory acute graft versus host disease (GvHD).1
The FDA has assigned a Prescription Drug User Fee Act (PDUFA) goal date of January 7, 2025, for remestemcel-L.
“We are pleased that FDA has accepted our BLA resubmission for review, and look forward to the potential approval of RYONCIL for children with SR-aGVHD,” Silviu Itescu, MBBS, FRACP, chief Executive Officer and Managing Director, Mesoblast, said in a statement.1
Mesoblast resubmitted its BLA for remestemcel-L on July 8, 2024, after 2 prior BLA submissions.2 In March 2024, the FDA informed Mesoblast that the available data from the phase 3 MSB-GVHD001 clinical trial (NCT02336230), including new requested Chemistry, Manufacturing, and Control (CMC) information previously requested, were sufficient for a BLA resubmission. The new data provided further evidence from potency assays demonstrating a suitable link between product used for the pediatric indication to the adult indication.3
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. This marked the second CRL Mesoblast had received for the therapy after originally submitting a BLA in 2020.4 Mesoblast had a Type A meeting with the FDA in September 2023 that led to plans including conducting an additional single-arm trial.5
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"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,” Itescu said in an earlier statement.5 “ 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 previously announced data from the phase 3 trial were released in November 2022 and demonstrated the long-term survival benefit in treated children through 4 years. These children had an overall survival (OS) rate of 63% at 1 year, 51% at 2 years, and 49% at 4 years (median, 2-3 years) in comparison to recently published control data in children and adults (using best available therapy or ruoxitinib for adults) in which OS rate was 40-49% at 1 year and 25-38% at 2 years (median, 6.5-11.1 months). The comparison also favors the study cohort, since 88% of these children had severe disease with the highest mortality risk, defined by either IBMTR Grade C/D or Glucksberg Grade 3/4, compared to 22% to 68% of patients in control studies having severe disease.5
“These exciting long-term results provide further evidence of remestemcel-L’s potential as a highly effective treatment for SR-aGVHD in children” principal investigator Joanne Kurtzberg, MD, Jerome Harris Distinguished Professor of Pediatrics and Professor of Pathology, Duke University Medical Center, commented on the data.6 “Responses are durable, reducing mortality of this often lethal complication of hematopoietic stem cell transplantation.”
