Core Insights - Agios Pharmaceuticals has received FDA approval for AQVESME™ (mitapivat), the first oral pyruvate kinase activator for treating anemia in adults with alpha- or beta-thalassemia, making it the only FDA-approved treatment for both non-transfusion-dependent and transfusion-dependent forms of the disease [1][3][4] Group 1: FDA Approval and Clinical Trials - The FDA approval is based on the results from the ENERGIZE and ENERGIZE-T Phase 3 trials, which included 452 patients and demonstrated significant improvements in hemolytic anemia, hemoglobin levels, and fatigue compared to placebo [2][9][10] - The ENERGIZE trial involved 194 non-transfusion-dependent patients, while the ENERGIZE-T trial included 258 transfusion-dependent patients, both showing positive efficacy endpoints [10][11] Group 2: Impact on Thalassemia Community - The approval of AQVESME is seen as a landmark moment for the thalassemia community, providing a new treatment option for approximately 6,000 adult patients in the U.S. who suffer from this debilitating disease [2][8] - The introduction of AQVESME is expected to address the urgent needs of patients, particularly in reducing the need for regular blood transfusions and improving quality of life [3][4] Group 3: Safety and Risk Management - Due to the risk of hepatocellular injury, AQVESME will be available only through a Risk Evaluation and Mitigation Strategy (REMS) program, which includes regular liver function tests and education for patients and healthcare providers [14][15][18] - In clinical trials, 5 patients experienced adverse reactions suggestive of hepatocellular injury, with 2 requiring hospitalization, highlighting the importance of monitoring liver health during treatment [17][19] Group 4: Market Availability - AQVESME is expected to be available in the U.S. by late January 2026, following the implementation of the REMS program [4][5] - The drug will be marketed under the AQVESME brand name for thalassemia, while continuing to be marketed as PYRUKYND® for PK deficiency, which does not require a REMS program [4][5]

Core Viewpoint - Agios Pharmaceuticals has received a positive opinion from the CHMP of the EMA for the new indication of PYRUKYND® (mitapivat) to treat anemia associated with both transfusion-dependent and non-transfusion-dependent alpha- or beta-thalassemia in adults [1][2][3] Company Developments - The CHMP's opinion is based on results from the global, randomized, double-blind, placebo-controlled ENERGIZE-T and ENERGIZE Phase 3 trials [2] - Agios has entered into an exclusive agreement with Avanzanite Bioscience B.V. for the commercialization and distribution of PYRUKYND across the European Economic Area, the UK, and Switzerland [3] - PYRUKYND has already received approval in Saudi Arabia for treating adult patients with both types of thalassemia [4] Clinical Trials - The ENERGIZE trial involved 194 non-transfusion-dependent patients, with a primary endpoint of achieving a hemoglobin response defined as an increase of ≥1.0 g/dL [10] - The ENERGIZE-T trial included 258 transfusion-dependent patients, focusing on a transfusion reduction response defined as a ≥50% reduction in transfused RBC units [11] Disease Background - Thalassemia is a rare inherited blood disease affecting hemoglobin production, categorized into alpha-thalassemia and beta-thalassemia [6] - An estimated 18,000 to 23,000 individuals are living with thalassemia in the U.S. and the five largest European countries [8]