The approval concludes what has been a difficult regulatory path for Ryoncil, which suffered FDA rejections in 2020 and 2023.
The FDA on Wednesday signed off on Mesoblast Limited’s remestemcel-L, now to be marketed as Ryoncil, for the treatment of steroid-refractory acute graft-versus-host disease in patients 2 months of age and up.
According to the Australian biotech, Ryoncil is the “first mesenchymal stromal cell (MSC) therapy” approved in the U.S.
Graft-versus-host disease (GVHD) is a complication that typically develops in patients who have undergone allogeneic stem cell transplantation. The condition arises when the grafted cells recognize the host’s cells as foreign and attack them, leading to hallmark symptoms such as rashes, itching, pain and diarrhea. In some cases, the symptoms can become severe enough to necessitate hospital intervention or even lead to death.
GVHD is typically managed with immunosuppressive drugs or through steroid treatments. Patients who are refractory or otherwise unresponsive to steroids often experience “wide-ranging health consequences, including damage to multiple organs, reduced quality of life and risk of death,” Nicole Verdun, director of the FDA’s Office of Therapeutic Products, said in a statement alongside the agency’s announcement of the approval.
Designed to be delivered intravenously, Ryoncil is comprised of mesenchymal stromal cells taken from the bone marrow of an unrelated donor. The treatment exerts immunomodulatory effects that counteract the inflammation in GVHD. According to Mesoblast CEO Silviu Itescu, Ryoncil’s approval on Wednesday provides an “important new treatment to children and families with no other acceptable options.”
The FDA approval is backed by data from a Phase III single-arm, multicenter trial, which found that at 28 days, Ryoncil had an overall response rate of 70% in pediatric patients with steroid-refractory acute GVHD, including 30% who hit complete response, according to the FDA. Ryoncil was also safe, with the most common side effects being infections, hemorrhage, fever and abdominal pain.
The FDA recommends that physicians closely monitor Ryoncil infusions and discontinue treatment if the patient develops signs of dyspnea, hypotension, fever, tachypnea, cyanosis or hypoxia.
Ryoncil’s path to approval has been long and fraught. The cell therapy suffered its first rejection in October 2020, with the FDA at the time asking for at least one more randomized controlled trial to establish its efficacy. Mesoblast filed a resubmission in early 2023, providing long-term survival data spanning at least four years, on top of additional data obtained from high-risk patients.
Later that year, in August 2023, the FDA again rejected Ryoncil, asking for even more data in adult patients.
