On November 3, 2025 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a commercial-stage biopharmaceutical company focused on delivering innovative medicines for patients with rare diseases, reported that new data on mitapivat, an oral pyruvate kinase (PK) activator, will be featured in oral and poster presentations during the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH 2025) in Orlando, Florida, December 6-9, 2025.
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"This year’s presentations at ASH (Free ASH Whitepaper) highlight the growing momentum of our PK activation franchise, featuring new clinical and preclinical data that reinforce the therapeutic potential of mitapivat for patients with thalassemia, sickle cell disease, and PK deficiency – debilitating and life-threatening rare blood disorders with few or no treatment options," said Sarah Gheuens, M.D., Ph.D., Chief Medical Officer and Head of R&D, Agios. "Building on these findings, we are also sharing research led by two of our advisory councils, each comprised of patients, caregivers, advocates, and physicians, that deepens our understanding of these rare diseases and helps guide the development of critical studies and resources tailored to patient needs. ASH (Free ASH Whitepaper) provides a vital platform to showcase this important body of data and strengthen our connections with the hematology and rare disease communities."
Select presentations and publications at ASH (Free ASH Whitepaper) 2025 will include:
Two poster presentations on results from the ENERGIZE-T Phase 3 trial of mitapivat in adults with transfusion-dependent alpha- or beta-thalassemia.
The first is a subgroup analysis of patients with alpha-thalassemia, showing that 77.8% (7 of 9) of individuals in the mitapivat arm achieved the primary endpoint of transfusion reduction response, compared to 0% (0 of 3) in the placebo arm. Additionally, reductions in transfusion burden were observed in the mitapivat arm versus none in the placebo arm for all key secondary endpoints.
The second highlights long-term results from the 17 patients who achieved transfusion independence with mitapivat during the double-blind phase of ENERGIZE-T, showing that the mean duration of their longest transfusion-free period was 30.5 weeks, with a maximum of 84.3 weeks, across the double-blind and ongoing open-label extension periods.
An oral presentation with preclinical data from an investigator-led study demonstrating that mitapivat protects against cardiomyopathy (heart muscle disease) in a mouse model of beta-thalassemia, with this mechanism potentially linked to its activation of the PKM2 isoform (or variant) of the PK enzyme in the heart. Cardiomyopathy is a leading cause of morbidity and mortality in patients with hemolytic anemias.
A poster presentation with positive findings from the ACTIVATE-Kids Phase 3 trial of mitapivat in children aged 1 to <18 years with PK deficiency who are not regularly transfused. The trial met its primary endpoint, with the mitapivat arm showing a higher hemoglobin response rate compared to the placebo arm. Additionally, the mitapivat arm showed improvements in changes from baseline for hemoglobin concentration and markers of hemolysis (indirect bilirubin and lactate dehydrogenase) compared to the placebo arm. The safety results were consistent with the safety profile for mitapivat previously observed for adult patients with PK deficiency who are not regularly transfused.
Research from two Agios-supported advisory councils, each comprised of patients, caregivers, advocates, and physicians, that builds on clinical and preclinical findings to help advance the scientific understanding of rare blood disorders.
The first is a poster from the Thalassemia Advocacy Advisory Council, which showcases a global patient survey that identified key knowledge gaps about thalassemia, including awareness of complication risks at certain hemoglobin levels and the importance of regular monitoring in non-transfusion-dependent patients.
The second is a publication-only study from the Red Cell Revolution, which highlights interim results of a qualitative survey assessing the physical, mental, and emotional impact of fatigue across patients with thalassemia, sickle cell disease, and PK deficiency, with cognitive impairment reported as the most bothersome manifestation of fatigue.
In total, 10 presentations and publications led by Agios and external collaborators will be shared at ASH (Free ASH Whitepaper) 2025.
ASH 2025 Accepted Abstracts
Title Number Date/Time Presenter Acceptance
Thalassemia
Efficacy of Mitapivat in Patients with Transfusion-Dependent Alpha-Thalassemia: Subgroup Analysis from the ENERGIZE-T Trial 4699
Monday, December 8, 2025, 6:00 – 8:00 p.m. EST Ashutosh Lal, M.D., MBBS, University of California San Francisco Benioff Children’s Hospital Oakland Poster
Long-Term Transfusion-Free Duration and Impact on Transfusion-Related Burdens: Results from the Ongoing ENERGIZE-T Open-Label Extension Study of Mitapivat in Transfusion-Dependent Alpha- or Beta-Thalassemia 4697
Monday, December 8, 2025, 6:00 – 8:00 p.m. EST
Sujit Sheth, M.D., Weill Cornell Medicine
Poster
Ex Vivo Treatment by Mitapivat, an Allosteric Pyruvate Kinase Activator, Reduced Oxidative Stress to Support Terminal Erythropoiesis of Non-Transfusion Dependent Thalassemia Patients Due to β-Thalassemia/Hb E Disease 2916 Sunday, December 7, 2025, 6:00 – 8:00 p.m. EST
Thidarat Suksangpleng, Ph.D., Siriraj Hospital, Siriraj-Thalassemia Center, Mahidol University, Bangkok, Thailand Poster
Long-Term Mitapivat Treatment Improves Inflammatory Pro-Fibrotic Cardiomyopathy in a Murine Model of β-Thalassemia 727 Monday, December 8, 2025, 10:30 – 10:45 a.m. EST
Enrica Federti, Ph.D., University of Verona, Italy Oral
Sickle Cell Disease
Mitapivat Improves RBC Integrity by Reducing Membrane Ubiquitination Accumulation 1146
Saturday, December 6, 2025, 5:30 – 7:30 p.m. EST Kang Le, Ph.D., National Heart, Lung, and Blood Institute, National Institutes of Health Poster
Pyruvate Kinase Deficiency
Efficacy and Safety of Mitapivat in Pediatric Patients with Pyruvate Kinase Deficiency Who Are Not Regularly Transfused: Results from the Phase 3, Global, Randomized, Double-Blind, Placebo-Controlled ACTIVATE-Kids Trial 4654 Monday, December 8, 2025, 6:00 – 8:00 p.m. EST Satheesh Chonat, M.D., Emory University School of Medicine and Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta Poster
Disease Monitoring and Management Among Pediatric Patients with Pyruvate Kinase Deficiency: Real-World Practices from Pyruvate Kinase Deficiency Registries Prior to 2024 International Expert Guidelines 4454 Sunday, December 7, 2025, 6:00 – 8:00 p.m. EST Sule Unal, M.D., Hacettepe University, Ankara, Turkey Poster
Other
Understanding Health Literacy Among Patients with Thalassemia: Results from a Global Patient Survey by the Thalassemia Advocacy Advisory Council 6421 Monday, December 8, 2025, 6:00 – 8:00 p.m. EST Sujit Sheth, M.D., Weill Cornell Medical College
Poster
Qualitative Interviews Exploring the Patient Experience of Fatigue in Individuals with Sickle Cell Disease (SCD), Thalassemia, and Pyruvate Kinase (PK) Deficiency 7971
N/A Biree Andemariam, M.D., University of Connecticut Health Publication
Activation of Pyruvate Kinases by Mitapivat Potentially Rescues Ineffective Erythropoiesis in Models of Diamond Blackfan Anemia 1121 Saturday, December 6, 2025, 5:30 – 7:30 p.m. EST Jonathan de Wilde, M.D., Feinstein Institutes for Medical Research, Northwell Health Poster
Please refer to the ASH (Free ASH Whitepaper) 2025 website for full session details and data presentation listings, and visit the Agios booth (#1661) onsite.
About PYRUKYND (mitapivat)
U.S. INDICATION
PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency.
U.S. IMPORTANT SAFETY INFORMATION
Acute Hemolysis: Acute hemolysis with subsequent anemia has been observed following abrupt interruption or discontinuation of PYRUKYND in a dose-ranging study. Avoid abruptly discontinuing PYRUKYND. Gradually taper the dose of PYRUKYND to discontinue treatment if possible. When discontinuing treatment, monitor patients for signs of acute hemolysis and anemia including jaundice, scleral icterus, dark urine, dizziness, confusion, fatigue, or shortness of breath.
Hepatocellular Injury in Another Condition: In patients with another condition treated with PYRUKYND at a higher dose than that recommended for patients with PK deficiency, liver injury has been observed. These events were characterized by a time to onset within the first 6 months of treatment with peak elevations of alanine aminotransferase of >5× upper limit of normal (ULN) with or without jaundice. All patients discontinued treatment with PYRUKYND, and these events improved upon treatment discontinuation.
Obtain liver tests prior to the initiation of PYRUKYND and monthly thereafter for the first 6 months and as clinically indicated. Interrupt PYRUKYND if clinically significant increases in liver tests are observed or alanine aminotransferase is >5x ULN. Discontinue PYRUKYND if hepatic injury due to PYRUKYND is suspected.
Adverse Reactions: The most common adverse reactions including laboratory abnormalities (≥10%) in patients with PK deficiency were estrone decreased (males), increased urate, back pain, estradiol decreased (males), and arthralgia.
Drug Interactions:
Strong CYP3A Inhibitors and Inducers: Avoid concomitant use.
Moderate CYP3A Inhibitors: Do not titrate PYRUKYND beyond 20 mg twice daily.
Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there are no alternatives, adjust PYRUKYND dosage.
Sensitive CYP3A, CYP2B6, CYP2C Substrates Including Hormonal Contraceptives: Avoid concomitant use with substrates that have narrow therapeutic index.
UGT1A1 Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
P-gp Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
Hepatic Impairment: Avoid use of PYRUKYND in patients with moderate and severe hepatic impairment.
Please see full Prescribing Information for PYRUKYND.
(Press release, Agios Pharmaceuticals, NOV 3, 2025, View Source [SID1234659238])