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

FDA

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).

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 (CR) rate of 30% (95% CI, 18.0%-43.6%) and a partial response (PR) rate of 41% (95% CI, 27.6%-55.0%). The median duration of response from response at 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