Acute Graft Versus Host Disease

RYONCIL™ (remestemcel-L) is being developed for the treatment of acute graft versus host disease (aGVHD), a potentially life-threatening complication of an allogeneic bone marrow transplant (BMT).  Remestemcel-L is also being developed for other rare diseases.

Mesoblast’s Biologics License Application (BLA) for RYONCIL for the treatment of children with steroid-refractory aGVHD has been accepted for priority review by the United States Food and Drug Administration (FDA). The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of September 30, 2020, and if approved, Mesoblast will make RYONCIL immediately available in the United States.

Disease Indication and Patient Population

In patients who have received a BMT, donor cells may attack the recipient (the person receiving the transplant), causing aGVHD. The donor T-cell mediated inflammatory response involves secretion of TNF-alpha and INF-gamma, resulting in activation of pro-inflammatory T-cells and tissue damage in the skin, gut and liver which is often fatal.

According to the Center for International Blood and Marrow Transplant Research, there are approximately 30,0001 allogeneic BMTs globally per year for diseases including hematological cancers, with 25%2 of all cases in the pediatric population. Nearly 50% of all allogeneic BMT patients develop aGVHD3. Liver or gastrointestinal involvement occur in up to 40%4 of all patients with aGVHD and are associated with the greatest risk of death, with mortality rates of up to 85%5.

Currently, there are no products currently approved in the United States for treatment of steroid-refractory aGVHD in children under 12, and off-label options have demonstrated mixed efficacy with high toxicity. We believe there is a significant need for effective treatment with a favorable risk/benefit profile.


RYONCIL is an investigational therapy comprising culture-expanded mesenchymal stem cells derived from the bone marrow of an unrelated donor. It is administered to patients in a series of intravenous infusions. RYONCIL is believed to have immunomodulatory properties to counteract the inflammatory processes that are implicated in steroid-refractory aGVHD by down-regulating the production of pro-inflammatory cytokines, increasing production of anti-inflammatory cytokines, and enabling recruitment of naturally occurring anti-inflammatory cells to involved tissues.

Aggregated results from 309 children treated with RYONCIL were presented at the 2020 annual meeting of the American Society for Transplantation Cellular Therapy and the Center for International Blood & Bone Marrow Transplant Research (TCT). The data showed that treatment with RYONCIL across three separate trials resulted in consistent treatment responses and survival outcomes in children with steroid-refractory acute graft versus host disease (SR-aGVHD).

Key findings and conclusions were:

  • Consistent safety and efficacy were observed across the continuum from first-line treatment after steroid failure through the most challenging patients who received RYONCIL as salvage after exhausting all other options.

  • In the aggregated dataset, 204 of the 309 (66%) patients achieved an overall response at Day 28 following a four-week course of RYONCIL.

  • Results were consistent across all grades of disease, including most severe (IBMTR Grade C/D or Glucksberg Grade 3/4).

  • In the most severe patients (Grade C/D), who accounted for 82% of all treated patients, Day 28 overall response was 65%.

  • Overall response at Day 28 was strongly predictive of survival at Day 100 and Day 180.

  • Day 28 responders were more than twice as likely to survive as non-responders (84% vs 39% at Day 100, and 83% vs 38% at Day 180).

  • RYONCIL was well tolerated with no infusion-related toxicity and no identified safety concerns.



1CIBMTR, Decision resources GVHD Epi Nov 2012

2Number of hematopoietic stem cell transplants registered with the CIBMTR by US centers, 2008 – 2012, by year of transplant

3Decision resources Niche Markets and Rare diseases: GVHD Nov 2012

4Jacobsohn, David A and Vogelsang, Georgia B. Acute graft versus host disease. Orphanet J Rare Dis. 2007; 2: 35.

5Westin, Jason R. et al. Steroid-Refractory Acute GVHD: Predictors and Outcomes. Advances in Hematology.