Positive results from phase II portion of RISE UP pivotal study in sickle cell disease with both mitapivat dose arms achieving statistically significant hemoglobin response

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 III portion of the study.

“It gives me great satisfaction to see the positive results from the Phase II portion of the RISE UP study. Mitapivat has a high potential to address aspects of the disease of greatest concern to patients,” said Modupe Idowu, M.D., associate professor at The University of Texas Health Science Center at Houston and medical director of UT Physicians Comprehensive Sickle Cell Center, UT Houston. “Sickle cell disease is a complex and debilitating disease characterized by anemia, pain crises, fatigue, cognitive effects and more. The sickle cell community is in dire need of effective disease-modifying therapies – particularly novel oral therapies – to address these unmet needs. I look forward to continuing the Phase III RISE UP study and am hopeful this will deliver a potential new treatment option for sickle cell warriors.”

The data from the Phase II 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 III portion of the RISE UP study, which is expected to enroll 198 patients. The operationally seamless Phase II/III study design allows Agios to leverage and create efficiencies in the start and conduct of the Phase III portion of RISE UP, with a goal of enrolling the first patient in Q4 of this year, reporting the Phase III data in 2025 and potentially receiving U.S. approval in 2026.

Results for the Phase II portion of RISE UP were as follows: i. A total of 79 patients were enrolled in the Phase II 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. ii. 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 1 g/dL in average hemoglobin concentrations from Week 10 through Week 12 compared with baseline. iii. 46.2 percent of patients (n=12) in the 50 mg BID mitapivat arm and 50.0 percent of patients (n=13) in the 100 mg BID mitapivat arm achieved a hemoglobin response, compared to 3.7 percent of patients (n=1) in the placebo arm (2-sided p=0.0003 and 0.0001, respectively). iv. 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. v. 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. vi. There were no adverse events (AEs) leading to discontinuation in either the mitapivat or the placebo arms. vii. Of the 79 patients enrolled in the study, 73 continued into the Phase II open-label extension period.

Given the promising 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 III study. Agios plans to present a full analysis of the RISE UP Phase II data at an upcoming medical meeting.