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Reaching the end of a long road to approval, the first mesenchymal stromal cell (MSC) therapy for steroid-refractory acute graft-versus-host disease (GVHD) finally reached the FDA green light.

The of remestemcel-L (Ryoncil) specifies use in pediatric patients 2 months or older with steroid-refractory acute GVHD. The cellular therapy received a vote of confidence from the Oncologic Drugs Advisory Committee in 2020, despite questions regarding the product's consistency and the approval request's reliance on data from a single-arm clinical trial.

"Today's decision marks an important milestone in the use of innovative cell-based therapies to treat life-threatening diseases with devastating impacts on patients, including children," said Peter Marks, MD, PhD, director of the FDA's Center for Biologics Evaluation and Research (CBER), in a statement. "This first mesenchymal stromal cell therapy approval demonstrates the FDA's commitment to supporting the development of safe and effective products that could improve the quality of life for patients with symptoms that are unresponsive to other therapies."

The approval was granted to Australia-based Mesoblast.

"Steroid-refractory acute graft-versus-host disease is a devastating condition with an extremely poor prognosis," said Joanne Kurtzberg, MD, of Duke University in Durham, North Carolina, in a . "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."

Systemic steroids are standard acute GVHD prophylaxis in allogeneic hematopoietic stem cell transplantation (HSCT), but the condition evolves into a in as many as half of cases. Steroid-refractory acute GVHD "can have significant, wide-ranging health consequences, including damage to multiple organs, reduced quality of life, and risk of death in affected patients," said Nicole Verdun, MD, also of the CBER. The harmful process is driven by sustained, systemic immune activation.

According to its , remestemcel-L reduces systemic inflammation by way of immunomodulatory bioactivity inherent to MSCs. Mesoblast describes remestemcel-L as an off-the-shelf product derived from MSCs donated by unrelated healthy donors. A single donor can provide enough cells to treat 400 patients.

Support for the approval came from a involving children with steroid-refractory acute GVHD after allogeneic HSCT and no prior immunosuppressant treatment for acute GVHD. Patients received remestemcel-L twice a week for 4 weeks, and the primary endpoint was objective response at day 28, hypothesized to be at least 20% greater than the standard-of-care overall response of 45%.

The results showed that 16 (30%) patients achieved a complete response at day 28, and 22 (41%) others had partial responses, meeting prespecified criteria for a successful trial.

The most common adverse events were infections, fever, hemorrhage, edema, abdominal pain, and hypertension. Premedication with corticosteroids and antihistamines prior to infusion and monitoring for hypersensitivity reactions to remestemcel-L are required.

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