On November 5, 2024 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in cellular metabolism and pyruvate kinase (PK) activation pioneering therapies for rare diseases, reported that new data on mitapivat and tebapivat (AG-946), the company’s PK activators, will be featured in oral and poster presentations during the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, California from December 7-10, 2024 (Press release, Agios Pharmaceuticals, NOV 5, 2024, View Source [SID1234647692]).
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"These data we are presenting at ASH (Free ASH Whitepaper) reaffirm our confidence in our growing pipeline focused on improving red blood cell health," Sarah Gheuens, M.D., Ph.D., chief medical officer and head of R&D at Agios. "We will highlight the clinical progress of our two PK activators – mitapivat and tebapivat – in multiple rare blood disorders with high patient needs, including thalassemia, sickle cell disease and myelodysplastic syndromes. These advancements showcase the quality of science and potential novel solutions coming out of our research and development efforts."
Key presentations and publications at ASH (Free ASH Whitepaper) 2024 will include:
An oral presentation on results from the Phase 3 ENERGIZE-T study evaluating mitapivat in adults with transfusion-dependent alpha- or beta-thalassemia versus placebo. Alongside the positive results from the Phase 3 ENERGIZE study of mitapivat in non-transfusion-dependent alpha- or beta-thalassemia previously presented at the 2024 European Hematology Association (EHA) (Free EHA Whitepaper) Congress, these data support mitapivat’s potential as an oral, disease-modifying therapy across the full range of patients with thalassemia regardless of transfusion status.
A poster presentation of a Phase 1 study assessing the safety, tolerability, pharmacokinetics and pharmacodynamics of tebapivat in patients with sickle cell disease, providing further evidence that PK activation may have beneficial effects in this patient population.
A trial-in-progress publication that outlines the Phase 2b study evaluating the efficacy and safety of tebapivat in patients with anemia due to lower-risk myelodysplastic syndromes.
In total, 16 presentations and publications led by Agios and external collaborators will be shared at ASH (Free ASH Whitepaper) 2024.
ASH 2024 Accepted Abstracts
Title Number Date/Time Presenter Acceptance
Thalassemia
ENERGIZE-T: A Global, Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of Mitapivat in Adults with Transfusion-Dependent Alpha- or Beta-Thalassemia 409 Sunday, December 8, 2024; 9:30 AM PT Maria Domenica Cappellini, M.D., University of Milan, Italy Oral
PKM2 binds to the regulatory regions of Gata-1 and STAT5 in β-thalassemic mouse erythroblasts 410 Sunday, December 8, 2024; 9:45 AM PT Enrica Federti, Ph.D., University of Verona, Verona, Italy Oral
Ex vivo treatment by mitapivat, an allosteric pyruvate kinase activator, reduced hemolysis and reactive oxygen species in red blood cells of non-regularly transfused hemolytic anemic patients with β-thalassemia/Hb E disease 2479 Sunday, December 8, 2024; 6:00 – 8:00 PM PT Thidarat Suksangpleng, Ph.D., Siriraj Hospital, Mahidol University, Bangkok, Thailand
Poster
Thalassemia scenario in Brazil: A descriptive study 2310 Saturday, December 7, 2024; 5:30 – 7:30 PM PT Catherine Moura, M.D., MSc, Abrasta – Brazilian Thalassemia Association, São Paulo, SP, Brazil Poster
Understanding Health Literacy Among Patients With Thalassemia: A Global Patient Survey by the Thalassemia Advocacy Advisory Council Blood Nov. 2024 supplementary issue N/A Sujit Sheth, M.D., Weill Cornell Medicine, New York City, New York
Publication
Molecular characterization of HbH in Spain
Blood Nov. 2024 supplementary issue N/A Ana María Villegas, M.D., University Hospital Clínico San Carlos, Complutense University of Madrid, Madrid Spain Publication
Molecular characterization of NTDT in Spain Blood Nov. 2024 supplementary issue N/A Ana María Villegas, M.D., University Hospital Clínico San Carlos, Complutense University of Madrid, Madrid Spain Publication
Molecular characterization of TDT in Spain 2024 supplementary issue N/A Ana María Villegas, M.D., University Hospital Clínico San Carlos, Complutense University of Madrid, Madrid Spain Publication
Sickle Cell Disease
Results From A Phase 1 Study To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Tebapivat (AG-946) In Patients With Sickle Cell Disease 2496 Sunday, December 8, 2024; 6:00 – 8:00 PM PT
Julia Xu, M.D., MScGH, Vascular Medical Institute, University of Pittsburgh, Pittsburg, PA Poster
Dual Activation of PKR and PKM2 Reduced the Development of Fibrosis and Iron Deposition in a Sickle Cell Disease Nephropathy Mouse Model 1107 Saturday, December 7, 2024; 5:30 – 7:00 PM PT Trang Nguyen, ScB, Agios Pharmaceuticals, Inc., Cambridge, MA Poster
Mitapivat-Induced Improvements in RBC Deformability and Membrane Integrity in Patients with Sickle Cell Disease are Sustained During Extended Therapy 2491 Sunday, December 8, 2024; 6:00 – 8:00 PM PT Xunde Wang, Ph.D., National Institute of Health, Bethesda, MD Poster
Myelodysplastic Syndromes
A Phase 2B, Open-Label Multicenter Study of Tebapivat (AG-946), a Potent Pyruvate Kinase Activator, in Patients with Anemia due to Lower-Risk Myelodysplastic Syndromes Blood Nov. 2024 supplementary issue N/A Amer M Zeidan, Yale University School of Medicine and Yale Comprehensive Cancer Center, New Haven, CT Publication
Pyruvate Kinase Deficiency
Clinical Monitoring Practices Among Adult Patients with Pyruvate Kinase Deficiency Who Have Never Been Transfused 3696 Sunday, December 8, 2024; 6:00 – 8:00 PM PT Stefan W. Eber, M.D., Ph.D., M1 Private Clinic Munich, Munich, Germany Poster
Other
uRADAR: European Patients Referral Frame to Improve Access to New Drugs and Therapies in Ultra-Rare Anemia Disorders and Severe Hereditary Spherocytosis 794 Monday, December 9, 2024; 10:45 AM PT Mar Manu Pereira, Ph.D., Vall d’Hebron Barcelona Hospital, Barcelona, Spain Oral
PIEZO1 gain-of-function variants lead to alterations in late-stage erythropoiesis by enhancing enucleation rate 3837 Monday, December 9, 2024; 6:00 – 8:00 PM PT
Barbara Eleni Rosato, Ph.D., University of Naples Federico II, Naples, Italy Poster
A Multicenter, Single-Arm Phase 2 Trial of Mitapivat in Adult Patients with Erythrocyte Membranopathies and Congenital Dyserythropoietic Anemia Type II – Results from the 8-Week Dose-Escalation Period 3831 Monday, December 9, 2024; 6:00 – 8:00 PM PT Thomas Doeven, M.D., Center for Benign Hematology, Thrombosis and Hemostasis – Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands Poster
Please refer to the ASH (Free ASH Whitepaper) 2024 online program for full session details and data presentation listings and visit the Agios booth (#105) onsite.
Investor Event at ASH (Free ASH Whitepaper) 2024
Agios will host a live and webcast investor event with the company’s leadership team and medical experts. The event will take place on Monday, December 9, in San Diego, starting at 7:00 a.m. PT (10:00 a.m. ET). The webcast will be accessible on the Investors section of the company’s website (www.agios.com) under the "Events & Presentations" tab. The archived webcast will be available on the company’s website approximately two hours after the event.
About PYRUKYND (mitapivat)
PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency in the United States, and for the treatment of PK deficiency in adult patients in the European Union.
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.
Adverse Reactions: Serious adverse reactions occurred in 10% of patients receiving PYRUKYND in the ACTIVATE trial, including atrial fibrillation, gastroenteritis, rib fracture, and musculoskeletal pain, each of which occurred in 1 patient. In the ACTIVATE trial, 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 and Summary of Product Characteristics for PYRUKYND.