On May 14, 2025 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 the company’s PK activators, mitapivat and tebapivat, will be featured in oral and poster presentations during the 30th European Hematology Association (EHA) (Free EHA Whitepaper) Congress (EHA 2025) in Milan, Italy, June 12-15, 2025 (Press release, Agios Pharmaceuticals, MAY 14, 2025, View Source [SID1234653048]).
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"The clinical results and scientific insights being presented at EHA (Free EHA Whitepaper) add to the robust body of efficacy and safety data demonstrating the promise of PK activation in treating both adults and children with rare blood disorders," said Sarah Gheuens, M.D., Ph.D., Chief Medical Officer and Head of R&D, Agios. "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. We look forward to this important opportunity to share these new data and strengthen our collaboration with the global hematology community at EHA (Free EHA Whitepaper)."
Select presentations and publications at EHA (Free EHA Whitepaper) 2025 will include:
An oral presentation of results from the ACTIVATE-KidsT Phase 3 study of mitapivat in children aged 1 to <18 years with PK deficiency who are regularly transfused. The study showed a clinically meaningful reduction in transfusion burden with mitapivat, with a higher proportion of patients achieving the primary endpoint of transfusion reduction response compared to placebo, though the prespecified statistical criterion was not met. Safety results were consistent with the safety profile for mitapivat previously observed in adults with PK deficiency who are regularly transfused. The ACTIVATE-KidsT study, along with the positive ACTIVATE-Kids Phase 3 trial, represents the successful execution of Agios’ first pediatric clinical program.
An oral presentation of long-term data from the investigator-led ESTIMATE Phase 2 trial, an open-label study investigating mitapivat in patients with sickle cell disease. In the study, mitapivat showed sustained efficacy and tolerability over three years, including improvements in anemia, hemolysis, painful vaso-occlusive crises, and markers of kidney damage.
A poster presentation with preclinical data demonstrating that tebapivat reduced red blood cell sickling and adhesion in blood samples from sickle cell disease patients, highlighting its therapeutic potential in this patient population.
A preclinical publication examining expression patterns of PKM2, an isoform (or variant) of the PK enzyme. The study found that, compared with healthy controls, patients with myelodysplastic syndromes (MDS) have significantly reduced PKM2 expression in CD34+ hematopoietic stem cells, which may be implicated in the development of MDS. These findings further support the ongoing investigation of tebapivat in lower-risk MDS, as it activates PKM2 in addition to PKR (the PK isoform found in red blood cells).
In total, 14 presentations and publications led by Agios and external collaborators will be shared at EHA (Free EHA Whitepaper) 2025.
EHA 2025 Accepted Abstracts
Title Number Date/Time Presenter Acceptance
Thalassemia
Overall survival and morbidity among adults with thalassemia in England: A retrospective analysis using routinely collected healthcare data from 2008 to 2020 PS2183
Saturday, June 14, 2025, 6:30 – 7:30 PM CEST
Khaled M. Musallam, M.D., Ph.D., Burjeel Medical City, Abu Dhabi, United Arab Emirates
Poster
Impact of non-transfusion-dependent thalassemia on adult patients’ health-related quality of life and work productivity: A multi-region real-world survey PF1192
Friday, June 13, 2025, 6:30 – 7:30 PM CEST
Khaled M. Musallam, M.D., Ph.D., Burjeel Medical City, Abu Dhabi, United Arab Emirates
Poster
ENERGIZE-T/ENERGIZE: Roxyscan assesses pyruvate kinase activator’s effect on oxidative stress sensitivity in β-thalassemia patients PS2192
Saturday, June 14, 2025, 6:30 – 7:30 PM CEST
Eduard J. van Beers, M.D., Ph.D., University Medical Center of Utrecht, Netherlands Poster
Understanding health literacy among patients with thalassemia: Initial key learnings from a global patient survey by the Thalassemia Advocacy Advisory Council PB3545
N/A Maria Domenica Cappellini, M.D., University of Milan, Italy Publication
Sickle Cell Disease
Three-year safety, efficacy, and renal outcomes of mitapivat treatment in sickle cell disease: Results from a phase 2, open-label study S299
Thursday, June 12, 2025, 5:00 – 6:15 PM CEST Geoffrey Kuppens, University Medical Center Utrecht, Netherlands
Oral
Patient-reported vaso-occlusive events, their associated pain severity, and impact of sickle cell disease on fatigue and quality of life: A real-world survey in the United States PS2179
Saturday, June 14, 2025, 6:30 – 7:30 PM CEST
Oladipo Cole, M.D., University of Connecticut Health Center
Poster
Optimizing hydroxyurea therapy in sickle cell disease: Insights from metabolite detection, treatment response and clinical outcomes* PF1176
Friday, June 13, 2025, 6:30 – 7:30 PM CEST
Sigrid van der Veen, University Medical Center Utrecht, Netherlands
Poster
Ex-vivo activation of pyruvate kinase by tebapivat reduces sickling and red blood cell adhesion in sickle cell disease PS2170
Saturday, June 14, 2025, 6:30 – 7:30 PM CEST
Minke Rab, M.D., Ph.D., University Medical Center Utrecht, Netherlands
Poster
Pyruvate Kinase Deficiency
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 S296 Thursday, June 12, 2025, 5:00 – 6:15 PM CEST Rachael F. Grace, M.D., MMSc; Dana-Farber/Boston Children’s Cancer and Blood Disorder Center, Harvard Medical School Oral
Cardiac magnetic resonance observations in a patient with pyruvate kinase deficiency and beta-thalassemia trait treated with mitapivat – a case report PB3570 N/A Paolo Ricchi, M.D., Ph.D., Center for Rare Red Blood Cell Diseases, AORN A. Cardarelli, Naples, Italy Publication
Myelodysplastic Syndromes
PKM and PKLR mRNA expression in CD34+ cells derived from patients with myelodysplastic syndromes PB2748
N/A Erin Tsai, M.S., Agios Pharmaceuticals Publication
Other
SATISFY: Mitapivat in adults with erythrocyte membranopathies and congenital dyserythropoietic anemia type II: A EuroBloodNet, multicenter, single-arm, phase 2 study S297
Thursday, June 12, 2025, 5:00 – 6:15 PM CEST Thomas Doeven, M.D., University Medical Center Utrecht, Netherlands
Oral
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 PS2199
Saturday, June 14, 2025, 6:30 – 7:30 PM CEST
Richard van Wijk, Ph.D., University Medical Center Utrecht, Netherlands
Poster
PIEZO1 gain-of-function drives glycolytic imbalance in late-stage erythropoiesis: The potential of mitapivat therapy in dehydrated hereditary stomatocytosis PS2201 Saturday, June 14, 2025, 6:30 – 7:30 PM CEST Barbara Eleni Rosato, Ph.D., University of Naples, Italy Poster
*This investigator-sponsored trial is part of a larger project funded by Agios
Please refer to the EHA (Free EHA Whitepaper) 2025 online program for full session details and data presentation listings, and visit the Agios booth (#C04) 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.