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

Mitapivat in adults with non-transfusion-dependent α-thalassaemia or β-thalassaemia (ENERGIZE): a phase 3, international, randomised, double-blind, placebo-controlled trial. (PubMed, Lancet) - P3 | "Mitapivat could be a new oral treatment for adults with NTD α-thalassaemia or NTD β-thalassaemia by increasing haemoglobin concentration and improving fatigue."

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

Mitapivat for non-transfusion-dependent thalassaemia. (PubMed, Lancet) - No abstract available

Journal

UNDERSTANDING HEALTH LITERACY AMONG PATIENTS WITH THALASSEMIA: INITIAL KEY LEARNINGS FROM A GLOBAL PATIENT SURVEY BY THE THALASSEMIA ADVOCACY ADVISORY COUNCIL (EHA 2025) - P3 | "A bespoke, 12-15-minute survey was self-administered to adults (≥18 years) with a self-reported physician diagnosis of alpha (α)- or beta (β)-thalassemia, excluding those diagnosed with α- or β-thalassemia trait or those currently enrolled in mitapivat clinical trials (e.g. ENERGIZE [NCT04770753] or ENERGIZE-T [NCT04770779])... Health literacy plays a critical role in patient and caregiver understanding and management of rare diseases; empowering patients with the information they need to advocate for their own care is essential for improving outcomes. The novel Thalassemia AAC developed a collaborative framework to design and implement a global patient survey, with the aim of yielding insights that are meaningful and impactful to patients. Key learnings from this unique approach can serve as a valuable roadmap for addressing unmet needs in other rare disease communities."

Clinical • Anemia • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Rare Diseases

CARDIAC MAGNETIC RESONANCE INSIGHTS OF RIGHT VENTRICULAR FUNCTION IN PYRUVATE KINASE DEFICIENCY AND BETA-THALASSEMIA TRAIT UNDER MITAPIVAT THERAPY (EHA 2025) - "This case provides the first clinical evidence that mitapivat may have cardiovascular benefits, particularly in enhancing RV function in PK deficiency/beta-thalassemia trait patients. The improvements in RV strain suggest that mitapivat may mitigate chronic hemolysis-related hemodynamic consequences, potentially improving cardiovascular outcomes. Further studies are needed to confirm mitapivat's potential role in PHT and RV function."

Anemia • Beta-Thalassemia • Cardiovascular • Genetic Disorders • Hematological Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

ROXYSCAN ASSESSES PYRUVATE KINASE ACTIVATOR'S EFFECT ON OXIDATIVE STRESS SENSITIVITY IN ß-THALASSEMIA PATIENTS: AN ANCILLARY STUDY OF THE ENERGIZE/ ENERGIZE-T CLINICAL TRIALS (EHA 2025) - P3 | "Mitapivat improves RBC resilience to oxidative stress in NTDT and TDT patients. The RoxyScan outcome parameters T-POD and EIMin were associated with thalassemia, RBC age, PK activity, and improved upon mitapivat treatment. Further studies are warranted to clarify whether mitapivat effects in thalassemia are driven by RBC lifespan extension, erythropoiesis stimulation, or both."

Clinical • Oxidative stress • Anemia • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

PIEZO1 GAIN-OF-FUNCTION DRIVES GLYCOLYTIC IMBALANCE IN LATE-STAGE ERYTHROPOIESIS: THE POTENTIAL OF MITAPIVAT THERAPY IN DEHYDRATED HEREDITARY STOMATOCYTOSIS (EHA 2025) - "Taken together, these findings link several components of glycolysis to changes in erythroid differentiation caused by a prototypical PIEZO1 GoF mutation in DHS. Treatment with mitapivat fully rescued erythropoiesis defects of PIEZO1-KI cells in vitro, suggesting the potential benefits of modulating glycolysis with PK activation in DHS."

Anemia • Hematological Disorders • CD36 • ITGA4 • SCARB1 • TFRC

RED BLOOD CELL AGE DISTRIBUTION AND METABOLIC FEATURES IN HEREDITARY SPHEROCYTOSIS, HEREDITARY XEROCYTOSIS AND CONGENITAL DYSERYTHROPOIETIC ANEMIA – BASELINE RESULTS OF EXPLORATORY ANALYSIS FROM THE SATISFY STUDY (EHA 2025) - P2 | "Baseline RBC metabolic characteristics in HS, HX and CDAII patients show comparable age-dependent patterns of PK activity, ATP and 2,3-DPG levels, and p50. Interestingly, distinct differences in RBC age-distribution were observed for the groups. Fraction 4, with the lowest PK activity, was most pronounced in the HS group, further supporting potential benefits from PK activation therapy, as currently being evaluated in SATISFY clinical trial."

Anemia • Genetic Disorders • Hematological Disorders • SEC23B

EFFICACY AND SAFETY OF MITAPIVAT IN PEDIATRIC PATIENTS WITH PYRUVATE KINASE DEFICIENCY WHO ARE REGULARLY TRANSFUSED: RESULTS FROM THE PHASE 3 RANDOMIZED GLOBAL PLACEBO-CONTROLLED ACTIVATE-KIDST TRIAL (EHA 2025) - P3 | "In ACTIVATE-KidsT, mitapivat was generally well tolerated, and the safety profile was consistent with that observed for adults with PK deficiency. Clinically meaningful improvements were observed in a higher proportion of pts in the mitapivat arm than the placebo arm for transfusion reduction, transfusion-free, and normal Hb responses. Mitapivat is the first disease-modifying treatment with the potential to provide therapeutic benefit in this pt population."

Clinical • P3 data • Cough • Infectious Disease • Pediatrics • Respiratory Diseases

SATISFY: MITAPIVAT IN ADULTS WITH ERYTHROCYTE MEMBRANOPATHIES AND CONGENITAL DYSERYTHROPOIETIC ANEMIA TYPE II: A EUROBLOODNET, MULTICENTER, SINGLE-ARM, PHASE 2 STUDY (EHA 2025) - P2 | "In the primary analysis of the SATISFY study, mitapivat was generally well tolerated and demonstrated sustained improvements in hemoglobin, hemolytic markers, quality of life and disease burden, particularly in patients with HS, indicating potential clinical benefits in this patient population and support continued evaluation in this trial."

Clinical • P2 data • Anemia • CNS Disorders • Genetic Disorders • Hematological Disorders • Infectious Disease • Insomnia • Pain • Respiratory Diseases • Sickle Cell Disease • Sleep Disorder • HP • SEC23B

THREE-YEAR SAFETY, EFFICACY, AND RENAL OUTCOMES OF MITAPIVAT TREATMENT IN SICKLE CELL DISEASE: RESULTS FROM A PHASE 2, OPEN-LABEL STUDY (EHA 2025) - P2 | "By December 2024, 5 participants completed the PFDEP.At the end of the PFDEP (n=5), the median age was 24.1 years (range 20.1-62.4); 3 participants were female, 3 used hydroxyurea, and 3 had HbSS. Three-year mitapivat in SCD showed sustained efficacy, tolerability, and improvements in anemia, hemolysis, and VOCs/hospitalizations. Divergent tubular and glomerular trends suggest potential glomerular benefits, but larger studies are needed for confirmation."

Clinical • P2 data • Anemia • Cardiovascular • Genetic Disorders • Hematological Disorders • Infectious Disease • Pain • Pneumonia • Pulmonary Embolism • Respiratory Diseases • Sickle Cell Disease • KIM1

Efficacy and safety of pyruvate kinase activator in treating hemolytic anemias: a systematic review. (PubMed, Expert Rev Hematol) - "These studies involved 206 patients, 166 of whom received mitapivat and the rest received placebo...These agents significantly improved hemoglobin levels, markers of hemolysis, and hematopoietic response, offering a beneficial therapeutic option for various hemolytic conditions, including pyruvate kinase deficiency, sickle cell disease, and thalassemia. A protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) before study initiation, CRD42024598980."

Journal • Review • Anemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • HP

Avanzanite Announces Pan-European Partnership with Agios to Launch PYRUKYND in Rare Blood Disorders (Businesswire) - "Avanzanite Bioscience B.V...announced today an exclusive agreement with Agios Pharmaceuticals Inc...a Boston-based biotech company focused on the development and commercialization of rare disease medicines. Under the agreement, Avanzanite will commercialize and distribute PYRUKYND (mitapivat) across the European Economic Area, the UK and Switzerland....Over the next 12 months, the company will expand into 32 European countries, including new territories of Italy, France, the UK, Romania, and Spain."

Commercial • Genetic Disorders • Hematological Disorders

Exploring potential allosteric activators of pyruvate Kinase: Insights from molecular docking, DFT and dynamics simulation studies. (PubMed, Comput Biol Med) - "In the virtual screening of the Enamine and Asinex libraries of chemical compounds, ten compounds were identified as top candidates with superior docking affinities and binding free energies compared to the reference compound Mitapivat...ADMET analysis revealed favorable pharmacokinetic properties, with minor water solubility and distribution concerns. These findings support the potential of Z169572442 and Z432281300 as promising PK activators and lay the groundwork for further experimental validation, aiming to develop effective therapies for SCD."

Journal • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

AG348-C-026: A Study of Mitapivat in Participants With Sickle Cell Disease and Nephropathy (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Agios Pharmaceuticals, Inc. | Trial completion date: Dec 2027 ➔ Dec 2028 | Trial primary completion date: Nov 2025 ➔ May 2027

Trial completion date • Trial primary completion date • Genetic Disorders • Hematological Disorders • Renal Disease • Sickle Cell Disease • CST3

Long-term efficacy and safety of mitapivat in non-transfusion-dependent α- or β-thalassaemia: An open-label phase 2 study. (PubMed, Br J Haematol) - P2 | "Five patients (29%) had a grade ≥3 treatment-emergent adverse event; none were considered treatment related. Treatment with mitapivat was well tolerated, with a safety profile consistent with previous studies of mitapivat in pyruvate kinase deficiency."

Journal • P2 data • Beta-Thalassemia • Hematological Disorders

Agios to Highlight Pyruvate Kinase Activation Portfolio with New Data in Rare Blood Disorders at 30th EHA Congress | AGIO Stock News (Gurufocus) - "Agios Pharmaceuticals (AGIO), a leader in developing pyruvate kinase (PK) activators, is set to present comprehensive data on its pioneering therapies at the 30th European Hematology Association (EHA) Congress in Milan. The focus will be on the results of the ACTIVATE-KidsT Phase 3 study involving mitapivat, which demonstrated a clinically meaningful reduction in transfusion burden among children with PK deficiency, though it did not meet the pre-specified statistical criterion essential for regulatory approval. More promising, the ESTIMATE Phase 2 trial delivered encouraging long-term data showcasing mitapivat's sustained efficacy and tolerability over a three-year period in patients with sickle cell disease....Additionally, preclinical findings for tebapivat revealed its potential in reducing red blood cell sickling and adhesion in sickle cell disease samples, underscoring its promise as a therapeutic candidate."

P2 data • P3 data • Preclinical • Metabolic Disorders • Sickle Cell Disease

Agios to Highlight Pyruvate Kinase Activation Portfolio with New Data in Rare Blood Disorders at 30th EHA Congress (Agios Pharma Press Release) - "Agios Pharmaceuticals, Inc...announced that new data on the company’s PK activators, mitapivat and tebapivat, will be featured in oral and poster presentations during the 30th European Hematology Association (EHA) Congress (EHA 2025) in Milan, Italy, June 12-15, 2025...'The presentations span serious conditions with limited or no treatment options, including sickle cell disease, thalassemia, PK deficiency, and myelodysplastic syndromes, offering meaningful results that highlight the therapeutic potential of mitapivat and tebapivat.'"

Clinical data • Preclinical • Beta-Thalassemia • Myelodysplastic Syndrome • Sickle Cell Disease

DRIVE-PK: A Study of AG-348 in Adult Participants With Pyruvate Kinase (PK) Deficiency (clinicaltrials.gov) - P2 | N=52 | Completed | Sponsor: Agios Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion • HP

Key Upcoming Milestones & Priorities (GlobeNewswire) - "Thalassemia: Receive FDA regulatory decision for PYRUKYND for the treatment of adult patients with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia (PDUFA goal date is September 7, 2025). Continue progressing the review of regulatory applications with health authorities in the European Union, Kingdom of Saudi Arabia and United Arab Emirates; Sickle Cell Disease: Announce topline results from the Phase 3 RISE UP study of mitapivat in sickle cell disease in late 2025, with a potential U.S. commercial launch in 2026. Additionally, begin patient enrollment for the Phase 2 study of tebapivat in sickle cell disease in mid-2025."

Enrollment status • Launch US • P3 data: top line • PDUFA • Beta-Thalassemia • Sickle Cell Disease

Agios Reports First Quarter 2025 Financial Results and Recent Business Highlights (GlobeNewswire) - "PYRUKYND Revenues: Generated $8.7 million in net revenue for the first quarter of 2025, compared to $8.2 million in the first quarter of 2024. A total of 234 unique patients have completed prescription enrollment forms, representing an increase of 5 percent over the fourth quarter of 2024. A total of 136 patients are on PYRUKYND therapy, inclusive of new prescriptions and continued therapy, as compared to 130 patients at the end of the fourth quarter 2024."

Sales • Beta-Thalassemia • Sickle Cell Disease

Investigating the Mechanistic Effects of Mitapivat in Subjects With Sickle Cell Disease (clinicaltrials.gov) - P=N/A | N=6 | Active, not recruiting | Sponsor: National Heart, Lung, and Blood Institute (NHLBI) | N=20 ➔ 6

Enrollment change • Anemia • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

Identification of Mitapivat's In Vivo Metabolites in the Rat Model by Quadrupole-Time-of-Flight (Q-TOF) Mass Spectrometry. (PubMed, J Mass Spectrom) - "Oxidation, N-dealkylation, oxidation followed by dehydrogenation, and hydrolysis were the major Phase I metabolic pathways of mitapivat. The chief Phase II metabolism pathway was glucuronide conjugation of oxidised and amide hydrolysed metabolites of mitapivat."

Journal • Preclinical • Hematological Disorders

MITAPIVAT METABOLICALLY REPROGRAMS HUMAN BETA-THALASSEMIC ERYTHROBLASTS, INCREASING THEIR RESPONSIVENESS TO OXIDATION. (PubMed, Blood Adv) - "Collectively, our data support a protective effect of mitapivat in beta-thal erythropoiesis, an effect favored by its activation of persistently expressed PKR and PKM2. In addition to the anticipated benefits on energy metabolism, we report that mitapivat treatment mitigated the oxidative damage in beta-thal erythropoiesis, ensuring improved beta-thal erythroblast maturation and survival."

Journal • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • CD34 • PKM • PRDX2

Agios’ Phase 3 ACTIVATE-Kids Study of Mitapivat in Children with Pyruvate Kinase (PK) Deficiency Not Regularly Transfused Met Primary Endpoint (GlobeNewswire) - P3 | N=30 | ACTIVATE-Kids (NCT05175105) | Sponsor: Agios Pharmaceuticals, Inc. | "The analysis was performed using a range of relative borrowing from the adult ACTIVATE study, representing the prior degree of belief in the similarity of the treatment effect in the pediatric and adult populations. The pre-specified statistical criterion for the primary endpoint in ACTIVATE-Kids was met for all possible borrowing weights (ranging from 0 to 1). In addition, the pre-specified supportive analysis based on traditional methodology comparing the hemoglobin response rate for mitapivat versus placebo, provided further evidence that the primary endpoint was met. There were 31.6% (6/19) of patients in the mitapivat arm achieving a hemoglobin response compared to 0% (0/11) of patients in the placebo arm; the 95% confidence interval for the difference in hemoglobin response rates between mitapivat and placebo was >0 (95% CI=10.8% to 52.7%)."

P3 data • Anemia • Hematological Disorders

Agios Reports Fourth Quarter and Full Year 2024 Financial Results and Recent Business Highlights (GlobeNewswire) - "'Backed by a strong balance sheet and a highly experienced team, Agios is focused on maximizing the potential PYRUKYND launches in thalassemia and sickle cell disease in 2025 and 2026, respectively'...PYRUKYND Revenues: Generated $10.7 million in net revenue for the fourth quarter of 2024, a 20 percent increase from the third quarter of 2024, primarily driven by year-end stocking and adjustments to certain revenue reserves...Announce topline results from the Phase 3 RISE UP study of mitapivat in sickle cell disease in late 2025...Additionally, begin patient enrollment for the Phase 2 study of tebapivat in sickle cell disease in mid-2025. LR-MDS: Complete patient enrollment in the Phase 2b study of tebapivat for LR-MDS in late 2025. Early-Stage Pipeline: File an Investigational New Drug Application for AG-236, a siRNA targeting TMPRSS6 intended for the treatment of polycythemia vera, in mid-2025."

Commercial • Enrollment status • IND • Launch US • P3 data: top line • Anemia • Beta-Thalassemia • Hematological Disorders • Myelodysplastic Syndrome • Polycythemia Vera • Sickle Cell Disease