The U.S. Food and Drug Administration (FDA) has granted approval to Ryoncil (remestemcel-L-rknd), a mesenchymal stromal cell (MSC) therapy developed by Mesoblast, for the treatment of steroid-refractory acute graft-versus-host disease (SR-aGVHD) in pediatric patients aged 2 months and older. This marks the first FDA approval of an MSC therapy in the United States, offering a new treatment option for a life-threatening condition with limited alternatives.
Clinical Efficacy and Safety
Ryoncil's approval was supported by data from a multicenter, single-arm Phase III clinical trial involving 54 pediatric patients with SR-aGVHD following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The study participants received intravenous infusions of Ryoncil twice weekly for four weeks. The primary efficacy endpoint was the rate and duration of response to treatment 28 days after initiating Ryoncil.
The trial demonstrated that 30% of study participants achieved a complete response, while 41% experienced a partial response. The overall response rate was 70% at day 28, a measure that predicts survival in aGVHD. These results highlight Ryoncil's potential to significantly improve outcomes for children with SR-aGVHD, a condition where approximately half of patients do not respond to first-line steroid treatment.
Nicole Verdun, M.D., director of the Office of Therapeutic Products in CBER, noted that SR-aGVHD can have "significant, wide-ranging health consequences, including damage to multiple organs, reduced quality of life and risk of death in affected patients."
Mechanism of Action and Manufacturing
Ryoncil contains mesenchymal stromal cells (MSCs) isolated from the bone marrow of healthy adult human donors. MSCs are known for their immunomodulatory properties, which can help to suppress the immune system and reduce inflammation associated with GVHD. The therapy is administered via intravenous infusion, with the recommended dosage being twice weekly for four weeks.
Adverse Reactions and Contraindications
Common adverse reactions observed in clinical trials included infections, fever, hemorrhage, edema, abdominal pain, and hypertension. The FDA advises that Ryoncil infusions should be monitored by the treating physician, and treatment should be discontinued if any signs of a reaction occur, such as dyspnea, hypotension, fever, tachypnea, cyanosis, or hypoxia.
Ryoncil is contraindicated in patients with known hypersensitivity to dimethyl sulfoxide or porcine and bovine proteins. Premedication with corticosteroids and antihistamines is recommended prior to infusion to mitigate potential hypersensitivity reactions.
Impact and Future Directions
The approval of Ryoncil represents a significant advancement in the treatment of SR-aGVHD in pediatric patients. Peter Marks, M.D., Ph.D., director of the FDA's Center for Biologics Evaluation and Research (CBER), stated that 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."
Mesoblast is also exploring the potential of Ryoncil in treating other inflammatory conditions, including SR-aGVHD in adults and biologic-resistant inflammatory bowel disease. Additionally, the company is developing other MSC therapies for conditions such as heart failure and chronic lower back pain.
