The FDA has granted approval to Ryoncil (remestemcel-L), marking it as the first mesenchymal stromal cell (MSC) therapy to receive approval in the United States. Developed by Mesoblast Limited, this allogeneic bone marrow-derived cell therapy is indicated for the treatment of steroid-refractory acute graft versus host disease (SR-aGvHD) in pediatric patients aged 2 months and older. This approval addresses a critical unmet need in children who develop SR-aGvHD following allogeneic hematopoietic stem cell transplantation (HSCT).
Clinical Efficacy and Safety
The FDA's decision was supported by data from a multicenter, single-arm, phase 3 trial (MSB-GVHD001) involving 54 pediatric patients with SR-aGVHD after allo-HSCT. Participants received intravenous infusions of Ryoncil twice weekly for four weeks. The primary endpoint, overall response rate (ORR) at day 28, was 70% (95% CI, 56.4%-82.0%), including a complete response rate of 30% and a partial response rate of 41%. The median duration of response was 54 days (range, 7 to 159+).
According to Dr. Joanne Kurtzberg, a transplant physician at Duke University Medical Center, "Steroid-refractory acute graft versus host disease is a devastating condition with an extremely poor prognosis. From today we are able to offer RYONCIL, the first FDA-approved treatment which will be life saving for so many children and will have a great impact on their families."
Common adverse reactions included infections, fever, hemorrhage, edema, abdominal pain, and hypertension. The recommended dose is 2 x 106 MSC/kg body weight per intravenous infusion, administered twice weekly for four weeks.
Addressing Unmet Needs in SR-aGVHD
Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic HSCT, where donor immune cells attack the recipient's tissues. Systemic steroids are the standard first-line treatment, but approximately half of patients do not respond, progressing to SR-aGVHD. This condition can lead to significant health consequences, including organ damage, reduced quality of life, and increased mortality.
Mechanism of Action
Remestemcel-L reduces systemic inflammation through the immunomodulatory bioactivity of MSCs. It is an off-the-shelf product derived from MSCs donated by unrelated healthy donors, with a single donor providing enough cells to treat 400 patients.
Regulatory Context and Future Directions
The FDA granted Ryoncil Orphan Drug, Fast Track, and Priority Review designations. Mesoblast is also developing Ryoncil for other inflammatory diseases, including SR-aGVHD in adults and biologic-resistant inflammatory bowel disease. The company is committed to working with the FDA to expand the indications for Ryoncil and advance its other late-stage products.
Dr. Silviu Itescu, Chief Executive of Mesoblast, stated, "With RYONCIL approval by FDA, Mesoblast has demonstrated the ability to bring the first MSC product to market. We will continue to work closely with FDA to obtain approval of our other late-stage products, including REVASCOR for cardiovascular diseases and rexlemestrocel-L for inflammatory pain indications, as well as expanding the indications for RYONCIL in both children and adults with inflammatory conditions."
