Mesoblast has said that clinically meaningful outcome in NIH trial of MPC-150-IM for heart failure left ventricular assist device (LVAD) recipients offers pathway for potential regulatory approval.
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The 159-patient randomized, sham-controlled phase 2 trial in end-stage heart failure patients implanted with a LVAD showed that Mesoblast’s allogeneic cell therapy candidate MPC-150-IM achieved significant reduction in major gastrointestinal (GI) bleeding episodes and related hospitalizations.
The clinically meaningful outcome confirms results seen in an earlier 30-patient pilot trial which provided the basis for the Regenerative Medicine Advanced Therapy (RMAT) designation granted to Mesoblast by the US Food and Drug Administration (FDA) for MPC-150-IM as adjunctive therapy to LVAD implantation.
As per the RMAT designation, Mesoblast received specific guidance from FDA that reduction in major GI bleeding episodes and related cases for hospitalizations in the current trial is a meaningful outcome. It is also claimed to be a high unmet need that could meet requirements for an approvable regulatory endpoint.
But, the FDA advised that the primary endpoint in the current trial of temporary weaning from full LVAD support is considered a biomarker and is not a clinically meaningful outcome in and of itself.
The trial was sponsored by results from the United States National Heart, Lung and Blood Institute (NHLBI), and the study was headed by University of Michigan Medical Center Adult Heart Transplant Program Surgical Director and Center for Circulatory Support, Program Director Francis Pagani.
Pagani said: “This trial, like the previous pilot investigation, demonstrated that intramyocardial allogeneic MPC injections were associated with a significant reduction in GI bleeding, a major cause of morbidity and increased cost in LVAD patient management.”
During the six month observation period, the MPC-150-IM showed that the primary endpoint of temporary weaning from full LVAD support was not achieved overall and it was limited the high rate of pump thrombosis reduced the number of evaluable wean attempts
Significant beneficial effects were observed on the primary endpoint of temporary weaning from full LVAD support in a pre-determined subgroup analysis of ischemic heart failure patients and it represented 44% of the total trial population (rate ratio 1.55, p value for interaction =0.02)
Reduction in cumulative incidence of major GI bleeding events by 48%, from 33% in controls to 17% (p=0.02) was observed.
Reduction in the rate of major GI bleeding events by 76%, from 15.9/100 patient months to 3.8/100 patient months (p<0.001) was observed.
Reduction was also observed in the rate of hospitalization for GI bleeding, a major cause of hospital readmissions, by 65%, from 0.21/100 patient months to 0.07/100 patient months (p=0.03); no significant reduction in all cause readmissions.
The overall time for transplant was similar between the two groups, despite a non-significant increase in anti-HLA class I antibodies in the MPC group (26% vs 9% in controls).
Mesoblast CEO Silviu Itescu said: “The clinically meaningful outcome achieved in these very high-risk patients provides a potential pathway to bring our heart failure product candidate MPC-150-IM to market sooner for these patients in great need.
“In addition, the ability to address inflammation and endothelial dysfunction, mechanisms central to the development and progression of heart failure, may have broader implications for the use of our cells in patients with advanced heart failure.”