The U.S. Food and Drug Administration (FDA) has approved remestemcel-L (Ryoncil, Mesoblast Ltd), a pioneering mesenchymal stromal cell (MSC) therapy for treating steroid-refractory acute graft-versus-host disease (SR-aGVHD) in children aged 2 months and older. This approval makes Ryoncil the first mesenchymal stromal cell therapy for GVHD to receive FDA authorization, marking a major milestone in cell-based therapies for this devastating disease.
The Role of Mesenchymal Stromal Cell Therapy
Mesenchymal stromal cell therapy for GVHD represents a promising new treatment for patients who do not respond to traditional steroid treatments. Each year, approximately 10,000 people in the U.S. undergo allogeneic bone marrow transplants, with 1,500 of them being children. Around 50% of these patients develop GVHD, and nearly half of those do not respond to steroids. Therefore, the FDA’s approval of Ryoncil offers a critical new option for these patients, potentially saving lives and improving outcomes for those suffering from this severe condition.
Peter Marks, MD, PhD, Director of the FDA’s Center for Biologics Evaluation and Research, emphasized the significance of this approval: “This approval marks an important milestone in the use of innovative cell-based therapies to treat life-threatening diseases with devastating impacts on patients, including children.”
The Clinical Trial Results
In a phase 3, multicenter, single-arm study, researchers evaluated the safety and effectiveness of Ryoncil in 54 children with SR-aGVHD following allogeneic hematopoietic stem cell transplantation. Participants received intravenous infusions of Ryoncil twice weekly for four consecutive weeks, totaling eight infusions.
To assess the severity and organ involvement of the disease, the study team used the International Blood and Marrow Transplantation Registry Severity Index (IBMTR). Notably, most participants (89%) had high-severity Grade C or D disease. After 28 days of treatment, 16 children (30%) achieved a complete response, while 22 children (41%) showed a partial response. These promising results were published in Biology of Blood and Marrow Transplantation.
Joanne Kurtzberg, MD, a transplant physician at Duke University Medical Center, noted the profound impact of this therapy, stating, “Ryoncil will be life saving for so many children and will have a great impact on their families.”
Safety Considerations for Mesenchymal Stromal Cell Therapy in GVHD
As with any advanced treatment, mesenchymal stromal cell therapy for GVHD carries some risks. Common adverse reactions include infections, fever, hemorrhage, edema, abdominal pain, and hypertension. Consequently, the FDA recommends that physicians closely monitor patients during Ryoncil infusions, with immediate cessation if adverse reactions such as dyspnea, hypotension, fever, tachypnea, cyanosis, or hypoxia occur.
Moreover, the FDA warns of possible complications, including hypersensitivity reactions, acute infusion reactions, transmission of infectious diseases, and ectopic tissue formation. In addition, Ryoncil is contraindicated in patients with known hypersensitivity to dimethyl sulfoxide or porcine and bovine proteins. Physicians should premedicate patients with corticosteroids and antihistamines prior to infusion and monitor for hypersensitivity reactions during treatment.
Availability of Mesenchymal Stromal Cell Therapy for GVHD
Ryoncil, which has received orphan-drug, fast-track, and priority-review status, will soon be available at transplant centers and other treating hospitals across the United States. This approval represents a critical advancement in the treatment of SR-aGVHD, particularly in pediatric patients, and provides a much-needed alternative for those with steroid-refractory disease.
To learn more about breakthroughs in mesenchymal stromal cell therapy for GVHD and other cell-based treatments, visit Stanford Physician Advocate.
The approval of mesenchymal stromal cell therapy for GVHD underscores the growing role of cell-based treatments in managing severe and resistant conditions. As the medical community continues to explore innovative options, therapies like Ryoncil offer new hope for patients suffering from GVHD. Consequently, ongoing research and clinical advancements are paving the way for more effective treatments and better outcomes for these vulnerable patients.