Agios says Phase 2 portion of RISE UP study meets primary efficacy endpoint

Agios Pharmaceuticals announced that the Phase 2 portion of the global RISE UP study of mitapivat in sickle cell disease met its primary endpoint of hemoglobin response for patients in both the 50 mg and 100 mg twice daily mitapivat arms. The safety profile for mitapivat observed in the study was generally consistent with previously reported data in other studies of sickle cell disease and other hemolytic anemias. Improvements were observed in markers of hemolysis and erythropoiesis and annualized rates of sickle cell pain crises at both mitapivat doses compared to placebo. These results support proceeding with the Phase 3 portion of the study.The data from the Phase 2 RISE UP study, representing the first placebo-controlled trial of mitapivat in sickle cell disease, underscore the potential of mitapivat to be a safe and effective oral treatment option for people living with sickle cell disease. Based on the data reported to date, Agios plans to proceed with the Phase 3 portion of the RISE UP study, which is expected to enroll 198 patients. The operationally seamless Phase 2/3 study design allows Agios to leverage and create efficiencies in the start and conduct of the Phase 3 portion of RISE UP, with a goal of enrolling the first patient in Q4 of this year, reporting the Phase 3 data in 2025 and potentially receiving U.S. approval in 2026. Results for the Phase 2 portion of RISE UP were as follows: A total of 79 patients were enrolled in the Phase 2 portion of the study, with 26 patients in the 50 mg BID mitapivat arm, 26 patients in the 100 mg BID mitapivat arm, and 27 patients in the placebo arm. Treatment with mitapivat demonstrated a statistically significant increase in hemoglobin response rate compared to placebo. Hemoglobin response was defined as an increase of greater than or equal to1 g/dL in average hemoglobin concentrations from Week 10 through Week 12 compared with baseline. 46.2 percent of patients in the 50 mg BID mitapivat arm and 50.0 percent of patients in the 100 mg BID mitapivat arm achieved a hemoglobin response, compared to 3.7 percent of patients in the placebo arm. Over the course of this 12-week study, the annualized rates of sickle cell pain crises for patients in the 50 mg BID and 100 mg BID mitapivat arms were 0.83 and 0.51, respectively, compared to 1.71 for patients in the placebo arm. The safety profile for mitapivat observed in the study was generally consistent with previously reported data in other studies of sickle cell disease and other hemolytic anemias. There were no adverse events leading to discontinuation in either the mitapivat or the placebo arms. Of the 79 patients enrolled in the study, 73 continued into the Phase 2 open-label extension period. Given the data for both mitapivat dose arms, the company will continue to analyze the study data over the coming weeks to select a dose for the Phase 3 study. Agios plans to present a full analysis of the RISE UP Phase 2 data at an upcoming medical meeting.