FDA authorizes remestemcel-L-rknd for pediatric steroid-refractory acute GVHD

On December 18, 2024, the Food and Drug Administration (FDA) granted approval for remestemcel-L-rknd, commercially known as Ryoncil, developed by Mesoblast, Inc. This therapy, derived from allogeneic bone marrow mesenchymal stromal cells (MSCs), is now authorized for treating steroid-refractory acute graft versus host disease (SR-aGVHD) in pediatric patients aged two months and older. This marks the first MSC therapy to receive FDA approval.

The approval is based on findings from a pivotal clinical trial, identified as MSB-GVHD001 (NCT02336230), which was a multicenter, prospective, and single-arm study. The study involved 54 pediatric patients who had SR-aGVHD following an allogeneic hematopoietic stem cell transplant (HSCT). Participants presented with SR-aGVHD of Grades B to D, excluding cases with only Grade B skin involvement as per the International Blood and Marrow Transplantation Registry Severity Index Criteria. SR-aGVHD was characterized by its failure to improve within a week or its progression within three days of treatment with methylprednisolone at a dose of 2 mg/kg/day or its equivalent. Patients who had received a second-line treatment for aGVHD before the screening were not included in the study.

The study's main efficacy metrics were the overall response rate (ORR) at 28 days and the duration of that response. The ORR, which combines complete and partial response rates, was recorded at 70% with a 95% confidence interval of 56.4 to 82.0. Specifically, the complete response rate was 30% (95% CI: 18.0, 43.6), and the partial response rate was 41% (95% CI: 27.6, 55.0). The median duration of the response, from the 28-day mark to progression, initiation of new systemic therapy for aGVHD, or any causative death, was found to be 54 days, with a range extending from 7 to 159+ days.

The most frequently reported non-laboratory adverse reactions, affecting 20% or more of participants, included viral and bacterial infections, unspecified pathogen infections, fever, bleeding, swelling, abdominal pain, and high blood pressure.

Ryoncil is administered at a recommended dose of 2 million MSCs per kilogram of body weight, delivered via intravenous infusion twice weekly over four weeks, totaling eight infusions. These infusions should be spaced at least three days apart. Depending on the patient’s response assessed at 28 days post-initial treatment, therapy may be continued.

Ryoncil has received several special designations from the FDA, including fast track, orphan drug, and priority review, underlining its importance and potential impact in treating serious conditions. These designations are part of the FDA’s expedited programs, which aim to facilitate the development and review of treatments for serious conditions.

Healthcare professionals are encouraged to report any serious adverse events related to medication use to the FDA’s MedWatch system. Additionally, for assistance with single-patient investigational new drug applications for oncology products overseen by the Center for Biologics Evaluation and Research, healthcare professionals can reach out to the relevant FDA department.