FDA accepts remestemcel-L BLA to treat steroid-refractory acute graft versus host disease

Mesoblast resubmits remestemcel-L BLA to treat steroid-refractory acute graft versus host disease | Image Credit: © Postmodern Studio - © Postmodern Studio - stock.adobe.com.

The Biologics License Application (BLA) for remestemcel-L (Ryoncil; Mesoblast Limited) has been accepted by the FDA as a potential treatment for children with steroid-refractory acute graft versus host disease (SR-aGVHD), according to a press release from Mesoblast Limited. With this acceptance, a Prescription Drug User Fee Act (PDUFA) date of January 7, 2025 has been set.¹

The filing of the BLA, which took place on July 8, 2024, followed the FDA informing Mesoblast that available clinical data from the phase 3 study, MSB-GVHD001, "appears sufficient to support submission of the proposed BLA for remestemcel-L for treatment of pediatric patients with SR-aGVHD," the company stated in the press release. The filing addresses the remaining chemistry, manufacturing, and control items.^1,2

“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, CEO, Mesoblast Limited, said in a statement.¹

In June 2024, the company announced a resubmission was in the works, following the issuance of a Complete Response Letter (CRL) from the FDA on August 4, 2023, at the time noting more data was needed to support the marketing approval.^3,4

At the time of CRL issuance, the FDA completed the Pre-License Inspection and did not issue any Form 483. No objectionable conditions were found, and the federal agency “acknowledged in the resubmission review that changes implemented appear to improve assay performance relative to the original version of the assay used in the pediatric phase 3 trial,” according to previous coverage on Contemporary Pediatrics.³

In a single-arm, phase 3 trial that enrolled 54 children with SR-aGVHD, a pre-specified primary outcome was met. In August 2020, the Oncologic Drugs Advisory Committee voted 9 to 1 in favor of remestemcel-L’s pediatric population efficacy. In September of the same year, the FDA noted that additional steps were needed for approval. The January 2023 BLA resubmission for remestemcel-L included long-term follow-up data from the Center for International Blood and Marrow Transplant Research phase 3 trial.³

Fifty-percent survival through 4 or more years during follow up in remestemcel-L-treated patients was observed in the phase 3 trial. According to Mesoblast, less than 20% survival was expected based on severity of disease. A post-hoc propensity matched study was also included in the resubmission, demonstrating that 6-month survival was 67% with remestemcel-L compared to 10% with other non-approved therapies.³

According to Mesoblast, the phase 3 trial took place across 20 centers in the Untied States where remestemcel-L was used as the first line of treatment for children who failed to respond to steroids for acute GVHD. The pre-specified primary endpoint, day 28 overall response (OR), was met, 70.4% vs 45% (P = 0.0003). An overall response at day 28 "was highly predictive of improved survival through day 100 (87% compared to 47% in patients that did not achieve day 28 OR P = 0.0001)," stated the company.¹

Compared to a matched control group of pediatric patients from the Mount SWinai Acute GVHD International Consortium (MAGIC) database, pediatric patients treated with remestemcel-L achieved higher day 28 OR (70% vs 43%), and higher day 100 survival (74% vs 57%).¹

"A propensity-matched study of outcomes in 25 children from Mesoblast’s Phase 3 trial and 27 control children who received best available treatment, including ruxolitinib, from the MAGIC database showed that 67% of high-risk children (MAP scores >0.29) who received Ryoncil achieved a Day 28 overall response and were alive after 180 days compared to just 10% in both categories in the MAGIC group," stated Mesoblast.¹

These results were demonstrated in highest-risk patients (identified using Mount Sinai Acute GVHD International Consortium). These data further support remestemcel-L use for the proposed study to treat high-risk adults with SR-aGVHD, stated Mesoblast.³

Remestemcel-L was granted Fast Track designation by the FDA, a process that facilitates development and expedited review of therapies for serious conditions that full unmet medical needs. The potential treatment was also granted Priority Review designation.¹

References:

1. FDA accepts Mesoblast’s BiologicS License Application (BLA) for Ryoncil in children with steroid-refractory acute graft-versushost disease (SR-aGVHD)
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). Mesoblast Limited. Press release. July 9, 2024. Accessed July 9, 2024. https://www.biospace.com/article/releases/mesoblast-resubmits-biologics-license-application-bla-with-united-states-food-and-drug-administration-fda-for-approval-of-ryoncil-in-children-with-steroid-refractory-acute-graft-versus-host-disease-sr-agvhd-/
3. Fitch, J. BLA for steroid-refractory acute graft versus host disease candidate to be resubmitted. Contemporary Pediatrics. June 4, 2024. Accessed July 9, 2024. https://www.contemporarypediatrics.com/view/bla-for-steroid-refractory-acute-graft-versus-host-disease-candidate-to-be-resubmitted
4. Fitch, J. FDA issues complete response letter to remestemcel-L for graft-versus-host disease treatment. Contemporary Pediatrics. August 10, 2023. Accessed July 9, 2024. https://www.contemporarypediatrics.com/view/fda-issues-complete-response-letter-to-remestemcel-l-for-graft-versus-host-disease-treatment