FDA

First mesenchymal stromal cell therapy approved for refractory acute GVHD

December 23, 2024

Brand name: Ryoncil

Generic name: remestemcel-L-rknd

Manufacturer: Mesoblast Limited

Approval date: December 18, 2024

FDA approved Ryoncil (remestemcel-L-rknd), an allogeneic (donor) bone marrow-derived mesenchymal stromal cell (MSC) therapy indicated for the treatment of steroid-refractory acute graft-versus-host disease (SR-aGVHD) in pediatric patients ≥2 months of age.

Ryoncil is the first FDA-approved MSC therapy. It contains MSCs, which have various roles in the body and can differentiate into multiple other types of cells. These MSCs are isolated from the bone marrow of healthy adult human donors.

Efficacy

Safety and effectiveness of Ryoncil were evaluated in the multicenter, single-arm MSB-GVHD-001 study (NCT02336230) involving 54 pediatric participants with SR-aGVHD after undergoing allogeneic hematopoietic stem cell transplantation. Participants received IV infusion of Ryoncil twice weekly for four consecutive weeks, for a total of eight infusions. Each participant’s condition at baseline was analyzed using the International Blood and Marrow Transplantation Registry Severity Index Criteria (IBMTR) to evaluate which organs have been affected and overall disease severity.

Ryoncil’s effectiveness was based primarily on the rate and duration of response to treatment 28 days after initiating Ryoncil. Study participants who had a partial or mixed response to treatment—defined as improved condition in one organ with either no change (partial) or worsening condition (mixed) in another organ—received additional infusions once weekly for an additional four weeks. Sixteen study participants (30%) had a complete response to treatment 28 days after receiving Ryoncil, while 22 study participants (41%) had a partial response.

Safety

Infusion of Ryoncil should be monitored by the treating physician, and the infusion should be discontinued if there is any evidence of a reaction which may include dyspnea, hypotension, fever, tachypnea, cyanosis, and hypoxia.

The most common adverse reactions in study participants were infections, fever, hemorrhage, edema, abdominal pain, and hypertension. Complications such as hypersensitivity and acute infusion reactions, transmission of infectious disease or agents, and ectopic tissue formation may occur.

Ryoncil is contraindicated in patients with known hypersensitivity to dimethyl sulfoxide or porcine and bovine proteins. Patients should be premedicated with corticosteroids and antihistamines prior to infusion and monitored for hypersensitivity reactions during treatment.

Recommended dose

The recommended dosage of Ryoncil is 2 x 10^6 MSC/kg body weight per IV infusion given twice per week for 4 consecutive weeks. Infusions should be administered at least 3 days apart. Response should be assessed 28 +/- 2 days after the first dose and further treatment should be administered as outlined in the Prescribing Information.

Sources:

FDA. (2024, December 18). FDA Approves First Mesenchymal Stromal Cell Therapy to Treat Steroid-refractory Acute Graft-versus-host Disease. [Press release]. https://www.fda.gov/news-events/press-announcements/fda-approves-first-mesenchymal-stromal-cell-therapy-treat-steroid-refractory-acute-graft-versus-host

Mesoblast Ltd. (2024, December 18). Mesoblast’s Ryoncil is the first U.S. FDA-approved mesenchymal stromal cell (MSC) therapy. [Press release]. https://investorsmedia.mesoblast.com/static-files/0c792a74-45f1-4b6f-b082-974bcb78f7c2

Mesoblast Ltd: Ryoncil (remestemcel-L). [Package insert]. U.S. Food and Drug Administration website. https://www.fda.gov/media/184603/download

Kurtzberg J, et al; MSB-GVHD001/002 Study Group. (2020, May). Biol Blood Marrow Transplant. A Phase 3, Single-Arm, Prospective Study of Remestemcel-L, Ex Vivo Culture-Expanded Adult Human Mesenchymal Stromal Cells for the Treatment of Pediatric Patients Who Failed to Respond to Steroid Treatment for Acute Graft-versus-Host Disease. https://pubmed.ncbi.nlm.nih.gov/32018062/