FDA Approves Remestemcel-L for Pediatric Steroid-Refractory Acute Graft-vs-Host Disease

The FDA has approved remestemcel-L-rknd (Ryoncil) for the treatment of pediatric patients 2 months of age and older with steroid-refractory acute graft-vs-host disease (SR-aGVHD).1

The regulatory decision was supported by data from the single-arm, phase 3 MSB-GVHD001 trial (NCT02336230). Findings showed that patients treated with remestemcel-L (n = 54) experienced an overall response rate (ORR) at day 28 of 70% (95% CI, 56.4%-82.0%), which included a complete response rate of 30% (95% CI, 18.0%-43.6%) and a partial response rate of 41% (95% CI, 27.6%-55.0%). The median duration of response from day 28 to progression, new systemic therapy for aGVHD, or death of any cause death was 54 days (range, 7 to 159+).

The most common nonlaboratory adverse effects reported in at least 20% of patients included viral infectious disorders, bacterial infectious disorders, infection – pathogen unspecified, pyrexia, hemorrhage, edema, abdominal pain, and hypertension.

The Road to Approval

FDA approval for remestemcel-L was initially sought in 2020; however, after the FDA granted priority review to the initial biologics license application (BLA) in April 2020, the FDA issued a complete response letter (CRL) in October of that year, requesting additional data from at least 1 randomized, controlled study in adult and/or pediatric patients with SR-aGVHD.2,3

In March 2023, the FDA accepted a BLA resubmission seeking the approval of remestemcel-L for pediatric patients with SR-aGVHD; however, the regulatory agency issued another CRL in August 2023, citing the need for more data to support the approval.4,5

A third BLA was accepted by the FDA in July 2024.6 The updated application addressed issues regarding chemistry, manufacturing, and control. It was also resubmitted after the FDA informed Mesoblast, the developer of remestemcel-L, that clinical data from MSB-GVHD001 could support the submission.

MSB-GVHD001 Overview

The single-arm, prospective MSB-GVHD001 trial enrolled pediatric patients between 2 months and 17 years of age with grade B to D aGVHD requiring systemic therapy with corticosteroids.7 Patients were required to have a lack of response to steroids, which was defined as progression within 3 days or no improvement within 7 days.

Grade B aGVHD with skin-only involvement precluded patients from enrolling. Any second-line therapy for aGVHD prior to enrollment was not allowed.

All patients received remestemcel-L at 2 x 106 MSCs/kg twice per week for 4 consecutive weeks. Doses were given at least 3 days apart and no more than 5 days apart. Eligible patients were then allowed to receive remestemcel-L once per week for 4 consecutive weeks, or twice per week for 4 consecutive weeks in the event of an aGVHD flare up.

ORR for remestemcel-L vs a prespecified ORR of 45% served as the trial's primary end point, which was met (P = .0003).6

References

1. FDA approves remestemcel-L-rknd for steroid-refractory acute graft versus host disease in pediatric patients. FDA. December 18, 2024. Accessed December 18, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-remestemcel-l-rknd-steroid-refractory-acute-graft-versus-host-disease-pediatric
2. FDA accepts Mesoblasts biologics license application for Ryoncil and agrees to priority review. News release. Mesoblast Limited. April 1, 2020. Accessed December 18, 2024. https://investorsmedia.mesoblast.com/static-files/1ee6fcd5-de79-4645-bc09-1f1fe8864047
3. Mesoblast receives complete response letter from the FDA for biologics license application for steroid-refractory acute graft versus host disease in children. News release. Mesoblast Limited. October 2, 2020. Accessed December 18, 2024. https://investorsmedia.mesoblast.com/static-files/1e259fcb-77ba-470c-91af-1c71e5fa32e0
4. FDA accepts Mesoblast’s resubmission of the biologic license application for remestemcel-L in children with steroid-refractory acute graft versus host disease as a complete response and sets goal date of August 2, 2023. News release. Mesoblast Limited. March 7, 2023. Accessed December 18, 2024. https://investorsmedia.mesoblast.com/static-files/d4c97ce2-fcba-4007-be6e-9d5e105a922a
5. Mesoblast receives complete response from US Food and Drug Administration for biologics license application for steroid-refractory acute graft versus host disease in children. News release. August 3, 2023. Accessed December 18, 2024. https://www.globenewswire.com/news-release/2023/08/04/2718706/0/en/Mesoblast-Receives-Complete-Response-From-U-S-Food-and-Drug-Administration-for-Biologics-License-Application-for-Steroid-Refractory-Acute-Graft-Versus-Host-Disease-in-Children.html
6. FDA accepts Mesoblast’s biologics license application (BLA) for Ryoncil in children with steroid-refractory acute graft-versus-host disease (SR-aGVHD). News release. Mesoblast Limited. July 23, 2024. Accessed December 18, 2024. https://investorsmedia.mesoblast.com/static-files/9a696437-abbb-4183-822f-9f74c1da5504
7. A prospective study of remestemcel-L, ex-vivo cultured adult human mesenchymal stromal cells, for the treatment of pediatric participants who have failed to respond to steroid treatment for acute graft-versus-host disease (aGVHD). ClinicalTrials.gov. Updated March 17, 2022. Accessed December 18, 2024. https://clinicaltrials.gov/study/NCT02336230