RARE Daily

FDA Rejects Mesoblast Treatment for GVHD in Kids Despite Panel’s Recommendation

October 2, 2020

Rare Daily Staff

The U.S. Food and Drug Administration said it would not approve Mesoblast’s experimental therapy remestemcel-L for the treatment of pediatric steroid-refractory acute graft versus host disease despite an advisory panel’s 9-1 vote in favor of approval.

The FDA in a complete response letter recommended that Mesoblast conduct at least one additional randomized, controlled study in adults and/or children to provide further evidence of the effectiveness of remestemcel-L for steroid-refractory acute graft versus host disease (SR-aGVHD). 

The FDA also identified a need for further scientific rationale to demonstrate the relationship of potency measurements to the product’s biologic activity. Assays measuring the potency of remestemcel-L will continue to be refined to provide further scientific rationale for its use in severe inflammatory diseases with high mortality risk, such as SR-aGVHD and COVID-19 ARDS.

Acute GVHD occurs in approximately 50 percent of patients who receive an allogeneic bone marrow transplant. Over 30,000 patients worldwide undergo an allogeneic bone marrow transplant annually, primarily during treatment for blood cancers, and these numbers are increasing. In patients with the most severe form of acute GVHD mortality is as high as 90 percent despite optimal institutional standard of care. There are currently no FDA-approved treatments in the United States for children under 12 with SR-aGVHD, a potentially life-threatening complication of an allogeneic bone marrow transplant for blood cancer.

Mesoblast’s lead allogeneic cell therapy product candidate, remestemcel-L, is an investigational therapy comprising culture-expanded mesenchymal stem cells derived from the bone marrow of an unrelated donor. Remestemcel-L is thought to have immunomodulatory properties to counteract the cytokine storms that are implicated in various inflammatory conditions 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.

As there are currently no approved treatments for this life-threatening condition in children under 12, Mesoblast will urgently request a Type A meeting with the FDA, expected within 30 days, to discuss a potential accelerated approval with a post-approval condition for an additional study.

Mesoblast is currently conducting a randomized, controlled phase 3 trial evaluating remestemcel-L in up to 300 ventilator-dependent adults with moderate to severe acute respiratory distress syndrome due to COVID-19. A second interim analysis by the trial’s independent Data Safety Monitoring Board is expected in early November, with completion of patient enrollment expected in December.

COVID-19 ARDS is an inflammatory disease with a similar profile of damaging inflammatory cytokines as is seen in children with SR-aGVHD and is the primary cause of death in COVID-19 infection. The trial’s primary endpoint is reduction of all-cause mortality within 30 days of randomization.

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