FDA Approves First MSC Therapy for Steroid-resistant Acute Graft-versus-host Disease

SILVER SPRING, Md., Dec. 18, 2024 — The U.S. Food and Drug Administration (FDA) has granted approval to Ryoncil (remestemcel-L-rknd), marking a significant advancement in the field of cell-based therapies. This groundbreaking allogeneic bone marrow-derived mesenchymal stromal cell (MSC) therapy is now approved for treating steroid-refractory acute graft-versus-host disease (SR-aGVHD) in children aged two months and older. Ryoncil is the first therapy of its kind to receive FDA approval, setting a precedent for future treatments in this category.

Ryoncil consists of MSCs, which have the ability to transform into a variety of cell types within the body. These cells are sourced from the bone marrow of healthy adult donors. Dr. Peter Marks, director of the FDA's Center for Biologics Evaluation and Research (CBER), emphasized the importance of this approval as a milestone in using innovative therapies to treat severe diseases that have a substantial impact on patients, particularly children. He highlighted the FDA's dedication to fostering the development of safe and effective treatments that could enhance the quality of life for patients unresponsive to other therapies.

Steroid-refractory acute graft-versus-host disease is a critical condition that can emerge following allogeneic hematopoietic stem cell transplantation (allo-HSCT), a procedure often conducted to treat certain blood cancers, disorders, or immune system diseases. This disease can result in extensive health complications, affecting multiple organs, diminishing quality of life, and increasing the risk of mortality for affected individuals. Dr. Nicole Verdun, director of the Office of Therapeutic Products in CBER, reiterated the FDA's ongoing commitment to addressing the significant unmet needs of those with severe and life-threatening conditions.

Ryoncil's safety and efficacy were established in a multicenter, single-arm study involving 54 pediatric patients with SR-aGVHD after undergoing allo-HSCT. Participants received Ryoncil infusions twice weekly over four weeks, totaling eight infusions. The study evaluated each patient's baseline condition using the International Blood and Marrow Transplantation Registry Severity Index Criteria, focusing on affected organs and the overall severity of the disease.

The primary measure of Ryoncil's efficacy was the response rate and duration 28 days post-treatment initiation. Participants exhibiting a partial or mixed response—indicating improvement in one organ with no change or worsening in another—were eligible for additional weekly infusions over four weeks. The study found that 30% of participants experienced a complete response, while 41% had a partial response 28 days after receiving Ryoncil.

During treatment, Ryoncil infusions must be monitored by healthcare professionals and discontinued upon any signs of adverse reactions, which may include symptoms such as dyspnea, hypotension, fever, tachypnea, cyanosis, and hypoxia. Common adverse effects reported in the study included infections, fever, hemorrhage, edema, abdominal pain, and hypertension. Patients need to be premedicated with corticosteroids and antihistamines to mitigate hypersensitivity risks.

Ryoncil holds contraindications for individuals with known hypersensitivity to dimethyl sulfoxide or porcine and bovine proteins. The FDA awarded Ryoncil Orphan Drug, Fast Track, and Priority Review designations, emphasizing its potential to address urgent and unmet medical needs. The approval was granted to Mesoblast, Inc., marking a pivotal step in the development of treatments for complex medical conditions.