Agios Announces Topline Results from RISE UP Phase 3 Trial of Mitapivat in Sickle Cell Disease

Core Insights - Agios Pharmaceuticals announced topline results from the RISE UP Phase 3 trial of mitapivat, an oral pyruvate kinase activator, for patients with sickle cell disease, demonstrating significant improvements in hemoglobin response and hemolysis markers [1][5][6] Trial Results - The trial met its primary endpoint of hemoglobin response, with 40.6% of patients in the mitapivat arm achieving a significant increase in hemoglobin levels compared to 2.9% in the placebo group [12] - Mitapivat showed a statistically significant improvement in average hemoglobin concentration and indirect bilirubin levels, but the reduction in annualized rate of sickle cell pain crises did not achieve statistical significance [2][3][12] - The safety profile of mitapivat was consistent with previous trials, with a similar proportion of adverse events reported in both mitapivat and placebo groups [19] Patient Outcomes - Patients who achieved hemoglobin response experienced clinically meaningful benefits in the annualized rate of sickle cell pain crises and hospitalizations, as well as improvements in fatigue scores [4][12][13] - The average change in PROMIS Fatigue score was -5.19 for hemoglobin responders, indicating a clinically meaningful improvement [13] Regulatory and Future Plans - Agios plans to engage with the FDA to discuss the findings and intends to submit a marketing application for mitapivat for sickle cell disease in early 2026 [15][16] - The company is also focused on the potential U.S. approval of PYRUKYND for thalassemia, anticipated in December 2025, and will take steps to reduce operating expenses [16] About Sickle Cell Disease - Sickle cell disease is a rare inherited blood disorder characterized by abnormal hemoglobin production, leading to severe complications and increased healthcare needs [18]