Pyrukynd (mitapivat) / Agios Pharmaceuticals, Avanzanite Bioscience, NewBridge Pharmaceuticals - LARVOL DELTA

Understanding and Targeting Metabolism in Erythrocyte Development and Disorders (ASH 2026) - "ATP requirements are also higher when red blood cells experience oxidative stress, for example in thalassaemia. Dr Franceschi will summarize extensive clinical trial data of the PK allosteric agonist, mitapivat, in the treatment of PK deficiency and other red blood cell diseases."

Beta-Thalassemia • Developmental Disorders • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome

Hemolysis Beyond Globin: Managing Inherited RBC Membrane and Enzyme Disorders (ASH 2026) - "Using pyruvate kinase deficiency as a model, he will review the emergence of targeted therapies such as mitapivat and their impact on hemoglobin levels, hemolysis, and transfusion burden...Although many of these approaches remain investigational, they signal an important shift toward mechanism-based treatment. Hanny Al-Samkari, M.D. Mass General Brigham Cancer Institute, Massachusetts General Hospital, Harvard Medical School Boston, MA Emerging Therapies for Treatment of Hereditary Hemolytic Anemias"

Hematological Disorders

Real-World Experience of Mitapivat in Pyruvate Kinase Deficiency. (PubMed, Am J Hematol) - No abstract available

Journal • Real-world evidence • Hematological Disorders

Mitapivat for transfusion-dependent α-thalassaemia and β-thalassaemia. (PubMed, Lancet) - No abstract available

Journal • Beta-Thalassemia

Efficacy and safety of mitapivat in adults with transfusion-dependent α-thalassaemia or β-thalassaemia (ENERGIZE-T): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. (PubMed, Lancet) - P3 | "Mitapivat significantly reduced the transfusion burden and was generally well tolerated, showing a favourable benefit-risk profile. These findings support mitapivat as the first oral disease-modifying therapy for adults with transfusion-dependent α-thalassaemia or β-thalassaemia, providing a new treatment option to reduce transfusion burden in this patient population."

Clinical • Journal • P3 data • Beta-Thalassemia • CNS Disorders • Fatigue • Infectious Disease • Insomnia • Pain • Respiratory Diseases • Sleep Disorder

Contemporary Management of Thalassemia: A Perspective on Current Standards and the Emergence of FDA-Approved Oral Therapy. (PubMed, Health Sci Rep) - "Searches included the terms "thalassemia," "mitapivat," "pyruvate kinase activator," "gene therapy," "hydroxyurea," and "luspatercept." Priority was given to recent systematic reviews, clinical practice guidelines, pivotal phase II and III clinical trials, regulatory publications, and peer-reviewed studies relevant to current therapeutic practice. Mitapivat represents a significant advance in thalassemia management by targeting erythrocyte metabolism and providing the first FDA-approved oral treatment for anemia in adults with α or β thalassemia. Multi-year follow-up and real-world studies are needed to further define its durability, safety, and role within evolving treatment strategies."

FDA event • Journal • Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Transplantation

2026 Update on Clinical Trials in β-Thalassemia. (PubMed, Am J Hematol) - "Luspatercept and mitapivat have demonstrated clinically meaningful improvements in hemoglobin levels and reduction of transfusion burden and are now approved in multiple jurisdictions. Additional pyruvate kinase activators, such as etavopivat, are undergoing clinical evaluation...Approved therapies, including betibeglogene autotemcel and exagamglogene autotemcel, have achieved high rates of durable transfusion independence, while emerging platforms aim to further improve efficacy, safety, and accessibility. At the same time, several promising approaches targeting fetal hemoglobin induction, iron metabolism, and ineffective erythropoiesis have failed to demonstrate sufficient clinical benefit despite preclinical proof of concept, highlighting the complexity of therapeutic development in β-thalassemia. Future priorities include refining patient selection, generating real-world and comparative effectiveness data, developing clinically meaningful response criteria, expanding..."

Journal • Beta-Thalassemia • Gene Therapies • Genetic Disorders • Pediatrics

From structural insight to molecule: Integrative molecular simulations identify candidate pyruvate kinase activators. (PubMed, PLoS One) - "Overall, CHEMBL3729403 and CHEMBL3729860 were identified as promising putative PKLR activators with improved predicted binding, stability, and pharmacokinetic properties compared with Mitapivat. These findings warrant further experimental validation to confirm their therapeutic potential in PKD and related metabolic disorders."

Journal • Metabolic Disorders • Oncology

Precision Medicine in Transfusion-Dependent and Non-Transfusion-Dependent β-Thalassemia: Toward Personalized Diagnosis and Therapy. (PubMed, Hemoglobin) - "Literature indexed in PubMed and Scopus from 2000 to 2025 was reviewed using terms related to thalassemia, precision medicine, magnetic resonance imaging (MRI), chelation tailoring, next-generation sequencing (NGS), fetal hemoglobin (HbF) modifiers, luspatercept, mitapivat, hepcidin, gene therapy, gene editing, and artificial intelligence (AI)...Personalized chelation should include deferiprone, either alone or in combination, when cardiac iron is increased...AI currently has its strongest role in screening and diagnosis, whereas risk-stratification models remain exploratory. Equitable implementation requires standardized TDT/NTDT pathways, regional MRI and genomics access, longitudinal registries, and multidisciplinary interpretation."

Journal • Review • Beta-Thalassemia • Gene Therapies • Genetic Disorders • Hematological Disorders • GDF15 • HBA2

Iron overload cardiomyopathy. (PubMed, Heart Fail Rev) - "Phlebotomy remains the cornerstone of treatment in primary haemochromatosis, while iron chelators, including deferoxamine, deferiprone and deferasirox, is the standard for transfusion-dependent patients. Novel disease-modifying or curative treatments for thalassaemia, such as luspatercept, mitapivat and gene therapy offer the prospect of addressing the root cause of iron loading. This review provides an updated comprehensive, evidence-based overview of the pathophysiology, diagnosis, and management of IOC."

Journal • Review • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Gene Therapies • Heart Failure • Hematological Disorders • Metabolic Disorders

A Study to Investigate the Effect of Mitapivat on Transfusion Burden in Subjects With Sickle Cell Disease (SCD) (clinicaltrials.gov) - P3 | N=159 | Recruiting | Sponsor: Agios Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

ENERGIZEKids: A Study to Investigate the Efficacy, Pharmacokinetics, and Safety of Mitapivat in Pediatric Participants With ?- or ?-Non-Transfusion-Dependent Thalassemia (clinicaltrials.gov) - P3 | N=45 | Recruiting | Sponsor: Agios Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Beta-Thalassemia • Genetic Disorders • Pediatrics • HP

ENERGIZEKids-T: A Study to Investigate the Efficacy, Pharmacokinetics, and Safety of Mitapivat in Pediatric Participants With Transfusion-Dependent Alpha- or Beta-Thalassemia (?- or ?-TDT) (clinicaltrials.gov) - P3 | N=54 | Recruiting | Sponsor: Agios Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Beta-Thalassemia • Genetic Disorders • Pediatrics

Second Quarter 2026 and Recent Corporate Highlights (The Manila Times) - "Mitapivat (PYRUKYND and AQVESME) delivered worldwide net revenues of $44.7 million in the second quarter of 2026, compared to $12.5 million in the second quarter of 2025...$40.9 million in U.S. net revenue and $3.8 million in ex-U.S. net revenue in the second quarter of 2026: U.S. net revenue was driven by the U.S. commercial launch of AQVESME (mitapivat) in thalassemia in late January 2026; Ex-U.S. net revenue reflected anticipated demand for PYRUKYND (mitapivat) in Europe following approval for thalassemia in May 2026, as well as continued, consistent early demand in Gulf Cooperation Council (GCC) countries."

Sales • Beta-Thalassemia • Sickle Cell Disease

Mitapivat (Aqvesme) for thalassemia. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Beta-Thalassemia • Genetic Disorders

Evaluating mitapivat for the treatment of alpha or beta thalassemia. (PubMed, Expert Opin Pharmacother) - "Mitapivat presents as a potential game-changer in the management of patients with both α- and β-thalassemia, regardless of transfusion dependency. However, further post-marketing evidence is required, in order to evaluate mitapivat profile under real world conditions and routine clinical practice."

Clinical • Journal • Review • Beta-Thalassemia • Genetic Disorders • Hematological Disorders

A Study to Investigate the Effect of Mitapivat on Transfusion Burden in Subjects With Sickle Cell Disease (SCD) (clinicaltrials.gov) - P3 | N=159 | Not yet recruiting | Sponsor: Agios Pharmaceuticals, Inc. | Trial completion date: Feb 2030 ➔ Aug 2030

Trial completion date • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Supportive care, prevention, and emerging therapies for acute chest syndrome in sickle cell disease. (PubMed, Expert Rev Hematol) - "This review synthesizes data on supportive measures (fluid management, analgesia, antibiotics, oxygen/respiratory support, and transfusion), preventive interventions (incentive spirometry and nocturnal bilevel positive airway pressure), disease-modifying therapies (hydroxyurea, L-glutamine), investigational agents (therapeutic anticoagulation, inhaled nitric oxide, and pyruvate kinase activators), and recently approved gene therapies (exagamglogene autotemcel, lovotibeglogene autotemcel)...Gene therapies represent a paradigm shift toward durable or potentially curative prevention of ACS. With expanding access to these therapies, ACS may become a rare complication of SCD, although significant barriers related to cost, infrastructure, and global equity must be overcome."

Journal • Gene Therapies • Genetic Disorders • Hematological Disorders • Pain • Preventive care • Sickle Cell Disease

Global research landscape and thematic transitions in pyruvate kinase deficiency: a decadal bibliometric analysis (2015-2025). (PubMed, Front Med (Lausanne)) - "Manual textual extraction of the 15 external PubMed records displayed precise semantic resonance with the core dataset's clusters, tracking a clear focus transition from baseline genotype mapping to targeted pyruvate kinase, R-type (PKR) activators (specifically mitapivat) and preclinical gene-editing interventions, without introducing divergent thematic anomalies. The analytical framework indicates that the PKD research domain is characterized by an evolving therapeutic focus, progressing from foundational descriptive epidemiology and supportive care toward mechanism-based, targeted interventions. Current empirical evidence highlights PKR allosteric activation as the most clinically developed cluster, while gene therapy represents an active, early-stage investigational frontier."

Journal • Review • Gene Therapies • Hematological Disorders • Rare Diseases

On July 07, 2026, Agios Pharmaceuticals AGIO received confirmation from the FDA regarding the acceptance of its supplemental new drug application for mitapivat, an oral pyruvate kinase activator being evaluated for the treatment of sickle cell disease. (Gurufocus) - "The FDA has granted priority review status, setting a target decision date of November 1 under the accelerated approval pathway."

FDA filing • PDUFA • Priority review • Sickle Cell Disease

A Study to Investigate the Effect of Mitapivat on Transfusion Burden in Subjects With Sickle Cell Disease (SCD) (clinicaltrials.gov) - P3 | N=159 | Not yet recruiting | Sponsor: Agios Pharmaceuticals, Inc.

New P3 trial • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Agios Showcases RISE UP Phase 3 Results at EHA 2026 Plenary Session Reinforcing Strong Anti-Hemolytic Profile of Mitapivat in Sickle Cell Disease (GlobeNewswire) - "New analyses from RISE UP show that mitapivat was associated with a clinically meaningful reduction in transfusion burden compared with placebo. Patients in the mitapivat arm had a 41.1% relative reduction in the proportion of patients requiring blood transfusions compared with placebo (23.9% with mitapivat vs. 40.6% with placebo), as well as a 55.9% relative reduction in average red blood cell units transfused per patient compared with placebo (0.70 units with mitapivat vs. 1.59 with placebo). These benefits were observed regardless of whether patients were also taking hydroxyurea. A reduction in transfusion burden in sickle cell disease can reflect decreased dependence on supportive care."

P3 data • Sickle Cell Disease

EFFICACY AND SAFETY OF PYRUVATE KINASE-R ACTIVATORS IN SICKLE CELL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS (EHA 2026) - "Three agents approved 2017–2019 briefly widened options, but crizanlizumab lost European approval in August 2023 (STAND trial: no VOC benefit), and voxelotor was withdrawn globally in September 2024 due to a fatal events imbalance the effectively resetting the field...Mitapivat (RISE UP) and etavopivat (HIBISCUS) have both completed Phase 2 RCTs in SCD, but their evidence has never been pooled...Baseline Hb was 8.4–8.8 g/dL across both trials, with 65–81% of participants receiving concomitant hydroxyurea...Abbreviations: CI, confidence interval; DL RE, DerSimonian-Laird random-effects model; Hb, haemoglobin; PP, per-protocol; PKR, pyruvate kinase-R; RR, risk ratio; SAE, serious adverse event; SCD, sickle cell disease; VOC, vaso-occlusive crisis; WMD, weighted mean difference; Wk, week. Panel A (Hb response) pooled estimate is exploratory given cross-trial heterogeneity in response definitions and timepoints; Panel C VOC rate ratio reflects HIBISCUS per-protocol..."

Retrospective data • Review • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

EFFECTS OF MITAPIVAT ON IRON BURDEN AND SPLEEN SIZE IN ERYTHROCYTE MEMBRANOPATHIES AND CONGENITAL DYSERYTHROPOIETIC ANEMIA TYPE II: 56-WEEK FOLLOW-UP RESULTS FROM THE SATISFY STUDY (EHA 2026) - P2 | "Summary/Conclusion Mitapivat treatment resulted in sustained Hb improvements, particularly in HS, along with reductions in ferritin concentration and, among responders, liver iron content, while spleen size remained unchanged. Further investigation in populations with higher iron burden and extended follow-up is warranted."

Anemia • Genetic Disorders • Hematological Disorders • HP • SEC23B

REAL-WORLD EXPERIENCE OF MITAPIVAT IN PYRUVATE KINASE DEFICIENCY (EHA 2026) - "Figure 1 - A: Median percentage change from baseline of hematologic parameters in the overall cohort and in responders to mitapivat. B: Median and IQR trends of hematologic parameters in responders to mitapivat."

Clinical • Real-world • Real-world evidence • Hematological Disorders • HP