Acute Graft Versus Host Disease

MSC-100-IV is being developed for the treatment of acute graft versus host disease (aGVHD) following an allogeneic bone marrow transplant (BMT). 

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 approved therapies for patients with acute steroid-refractory GVHD in the United States, 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.


MSC-100-IV is a Tier 1 intravenously delivered product candidate comprising 100 million mesenchymal stem cells (MSCs)/unit dose under investigation for the treatment of steroid refractory acute graft versus host diseases (aGVHD) following an allogeneic BMT.

Mechanism of Action

MSC-100-IV has demonstrated immunomodulatory properties to regulate T-cell mediated inflammatory responses by inhibiting T-cell proliferation and down-regulating the production of the pro-inflammatory cytokines, including tumor necrosis factor-alpha, or TNF-alpha, and interferon gamma.

Regulatory Approval and Clinical Trials

Product Registration - Japan

Our licensee in Japan for aGVHD, JCR Pharmaceuticals Co. Ltd., is marketing its MSC-based product for children and adults with aGVHD. TEMCELL® HS Inj.6 is the first allogeneic cellular medicine to receive full regulatory approval in Japan.

Expanded Access Program (EAP)

More than 240 pediatric patients suffering from steroid-refractory aGVHD have been treated with MSC-100-IV under an EAP in the United States, Canada and several European countries.

Ongoing Phase 3 Trial

Mesoblast is conducting a Phase 3 clinical trial of MSC-100-IV in pediatric patients with aGVHD following HSCT who have failed systemic corticosteroid therapy. Enrollment of 55 patients has been completed. 

The Phase 3 trial met the primary endpoint of Day 28 overall response in February 2018.  Based on interactions with the FDA, Mesoblast believes that successful results from the completed Phase 3 trial through Day 100, together with Day 180 safety and quality of life parameters in these patients, may provide sufficient clinical evidence for filing for MSC-100-IV in the United States under an accelerated approval pathway.

In November 2016, this Phase 3 trial was successful in a pre-specified interim futility analysis.

Additional information about this trial is available at: Phase 3 trial


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

6TEMCELL® HS Inj. is the registered trademark of JCR Pharmaceuticals Co. Ltd.