Agios Pharmaceuticals says Phase 3 ACTIVATE trial achieved primary endpoint

Agios Pharmaceuticals announced that the global Phase 3 ACTIVATE trial of mitapivat in adults with pyruvate kinase deficiency who do not receive regular transfusions met its primary endpoint. Treatment with mitapivat demonstrated a statistically significant, sustained increase in hemoglobin compared to placebo. The safety profile observed in the study was generally consistent with previously published data. Mitapivat is a first-in-class, investigational, oral, small molecule allosteric activator of wild-type and a variety of mutated PKR enzymes. Results from the ACTIVATE trial were as follows: 40 percent of patients randomized to mitapivat achieved a hemoglobin response, defined as a greater than or equal to1.5 g/dL increase in hemoglobin concentration from baseline that is sustained at two or more scheduled assessments at Weeks 16, 20 and 24 during the fixed-dose period, compared to 0 patients randomized to placebo. Treatment with mitapivat demonstrated statistically significant improvements over placebo across pre-specified key secondary endpoints, including average change from baseline in hemoglobin concentration at Weeks 16, 20, and 24 during the fixed-dose period; markers of hemolysis; and markers of hematopoietic activity. The safety profile observed in the study was generally consistent with previously reported data. There were no AEs leading to discontinuation in either the mitapivat or the placebo arm. Agios is conducting a full analysis of the ACTIVATE data, including patient-reported outcomes which are not yet available. The company expects to submit the complete results of the trial for presentation at the European Hematology Association Virtual Congress, which is being held June 9-17, 2021. Agios anticipates filing for U.S. and EU regulatory approval in adults with PK deficiency in 2021, with a potential 2022 commercial launch in both geographies.