FDA Approves First Mesenchymal Stromal Cell Therapy for Steroid-Refractory Acute Graft-versus-Host Disease

A significant step forward in regenerative medicine: the U.S. Food and Drug Administration (FDA) has approved Ryoncil (remestemcel-L-rknd) , an innovative therapy based on donor-derived mesenchymal stromal cells (MSCs). This therapeutic solution, indicated for the treatment of steroid-refractory acute graft-versus-host disease (SR-aGVHD) in pediatric patients aged two months and older, marks a milestone in the treatment of severe and often life-threatening clinical conditions.

Ryoncil stands out as the first FDA-approved MSC therapy. These mesenchymal stromal cells, isolated from the bone marrow of healthy adult donors, have the ability to transform into various types of cells, performing crucial roles in the human body.

An Innovation for Severe Diseases SR-aGVHD is a severe complication that can arise after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This type of transplant, used to treat certain forms of blood cancers, blood disorders, or immunological diseases, carries the risk that the transplanted cells will attack the recipient's body, causing organ damage, reduced quality of life, and, in severe cases, death.

Peter Marks , director of the FDA's Center for Biologics Evaluation and Research, emphasized the importance of this innovative approach: "This approval marks a pivotal moment for advanced cell therapies, offering new hope to patients, including children, for whom other treatments have proven ineffective."

What is SR-aGVHD? Graft-versus-host disease (GVHD) is a serious complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . This type of transplant, used to treat certain forms of blood cancers or other severe conditions, involves transferring stem cells from a healthy donor to the patient. However, the donor’s cells may recognize the recipient's body as foreign and attack its tissues. This attack can cause inflammation and damage to vital organs such as the liver, intestines, and skin.

When this disease is defined as steroid-refractory , it means that it no longer responds to standard treatments with corticosteroids, anti-inflammatory drugs used to control immune reactions. At this point, patients have very limited therapeutic options, with a high risk of fatal complications.

Steroids: What Are They and Why Are They Used? Steroids are a class of drugs used in multiple medical contexts. Corticosteroids , in particular, are synthetic substances similar to hormones naturally produced by the adrenal glands. Their primary functions include reducing inflammation and suppressing the immune system, preventing excessive reactions like those occurring in GVHD.

In GVHD treatment, steroids are the first-line intervention to calm the immune system’s attack. However, when the body becomes refractory, meaning resistant, the effectiveness of these drugs drastically decreases, leaving patients without effective alternatives.

The Ryoncil Therapy Ryoncil uses mesenchymal stromal cells (MSCs) derived from the bone marrow of healthy donors. These cells are known for their ability to:

Reduce inflammation. Modulate the immune system, preventing harmful attacks on healthy tissues. Promote the regeneration of damaged tissues. The safety and efficacy of Ryoncil were tested in a multicenter study conducted on 54 pediatric patients with SR-aGVHD. The participants received intravenous infusions of Ryoncil twice a week for four consecutive weeks, with the possibility of extending treatment based on individual response.

28 days after the start of therapy:

30% of patients showed a complete response, with resolution of symptoms. 41% had a partial response, showing improvement in some organs. The therapy was well tolerated but not without risks. The most common side effects included infections, fever, bleeding, swelling, and hypertension. Serious reactions such as respiratory difficulties, hypotension, or hypersensitivity reactions were closely monitored during infusions.

Why It Matters The approval of Ryoncil represents a fundamental advancement for pediatric patients, offering a new therapeutic option for a highly complex and difficult-to-treat condition.

Indications and Precautions Ryoncil is contraindicated in patients with known hypersensitivity to dimethyl sulfoxide or animal proteins (porcine or bovine). Pre-treatment with corticosteroids and antihistamines is required to prevent allergic reactions.

Thanks to the recognition of designations such as Orphan Drug , Fast Track , and Priority Review , the approval process was accelerated, highlighting the urgency and potential impact of this therapy.

Glossary Allo-HSCT : Allogeneic hematopoietic stem cell transplantation. A procedure where stem cells from a healthy donor are transferred to the patient. MSC : Mesenchymal stromal cells, cells capable of differentiating into various types of cells. GVHD (Graft-versus-host disease) : A post-transplant complication where donor cells attack the recipient's tissues. SR-aGVHD : Steroid-refractory acute graft-versus-host disease, an acute form of GVHD that does not respond to steroids. Corticosteroids : Drugs used to reduce inflammation and suppress the immune system. Allogeneic (donor) : From an individual different from the recipient. Orphan Drug : A drug designated to treat rare diseases. Ryoncil: Ryoncil is a biological treatment developed by Mesoblast Limited for steroid-refractory acute graft-versus-host disease (aGVHD) in pediatric patients. It is based on mesenchymal stem cells (MSCs) derived from the bone marrow of healthy, unrelated donors. These cells are infused intravenously to address the inflammatory processes associated with steroid-refractory aGVHD. On December 18, 2024, the U.S. Food and Drug Administration (FDA) approved Ryoncil as the first MSC-based therapy for the treatment of steroid-refractory aGVHD in children aged 2 months or older.