The US Food and Drug Administration (FDA) has approved remestemcel-L (Ryoncil, Mesoblast Ltd), an allogeneic bone marrow‒derived mesenchymal stromal cell (MSC) therapy for steroid-refractory acute graft-vs-host disease (SR-aGVHD) in children 2 months of age or older.
It’s the first MSC product approved by the FDA for any indication.
According to a new release from the company, roughly 10,000 patients undergo an allogeneic bone marrow transplant each year in the United States, 1500 of whom are children. About half develop aGVHD, and almost half of those do not respond to steroids. 
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,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an FDA statement.
The safety and effectiveness of Ryoncil were evaluated in a multicenter, single-arm phase 3 study of 54 children with SR-aGVHD after undergoing allogeneic hematopoietic stem cell transplantation.
Participants received intravenous infusion of Ryoncil twice weekly for four consecutive weeks, for a total of eight infusions.
They were evaluated at baseline using the International Blood and Marrow Transplantation Registry Severity Index Criteria (IBMTR) to evaluate which organs have been affected and the overall severity of the disease. Most (89%) had high-severity Grade C or D disease.
Ryoncil’s effectiveness was based primarily on the rate and duration of response to treatment 28 days after starting treatment.
Sixteen children (30%) had a complete response to treatment 28 days after receiving Ryoncil, while 22 (41%) had a partial response. The full results are published in Biology of Blood and Marrow Transplantation.
“Steroid-refractory acute graft versus host disease is a devastating condition with an extremely poor prognosis,” transplant physician Joanne Kurtzberg, MD, distinguished professor of pediatrics, and director, Marcus Center for Cellular Cures at Duke University Medical Center (DUMC), Durham, North Carolina, said in company news release.
Ryoncil “will be life saving for so many children and will have a great impact on their families,” said Kurtzberg, who worked on the phase 3 study.
The most common adverse reactions seen with Ryoncil were infections, fever, hemorrhage, edema, abdominal pain, and hypertension.
The FDA advises that infusions of Ryoncil be monitored by the treating physician and stopped if there is any evidence of a reaction, which may include dyspnea, hypotension, fever, tachypnea, cyanosis, and hypoxia.
“Complications such as hypersensitivity and acute infusion reactions, transmission of infectious disease or agents and ectopic tissue formation may occur following treatment with Ryoncil,” the FDA said.
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 with Ryoncil.
Ryoncil for SR-aGVHD had orphan-drug, fast-track, and priority-review status. It will be available in the United States at transplant centers and other treating hospitals, the company said.
