Slide 1: Effects of mitapivat on iron burden and spleen size: 56-week SATISFY results
Effects of mitapivat on iron burden and spleen size in patients with erythrocyte membranopathies and congenital dyserythropoietic anemia type II 56-Week follow-up results from the SATISFY study Thomas Doeven, MD, Eduard J. van Beers, MD, PhD, Richard van Wijk, Joline L. Saes, MD, PhD, Jesper B. Pete
Slide 2: Disclosures
Disclosures No conflicts of interest
Slide 3: Erythrocyte membranopathies and CDA II
Erythrocyte membranopathies and CDA II Hereditary anemias Hereditary spherocytosis Hereditary xerocytosis Congenital dyserythropoietic anemia type II 3 Figure created with biorender.com
Slide 4: Iron overload is a frequent complication associated with increased morbidity
Iron overload is a frequent complication and is associated with increased morbidity Van Beers et al. (2024) – Blood Advances Van Vuren et al. (2021) - Hemasphere
Slide 5: Treatment options for iron overload are limited
Treatment options for iron overload are limited Phlebotomy Iron chelation Figure created with biorender.com
Slide 6: Objectives of this follow-up analysis
Objectives of this follow-up analysis This analysis aims to evaluate the (long-term) effects of mitapivat on 1. Hemoglobin levels and hemolytic markers 2. Iron overload (iron markers and liver iron concentration) 3. Spleen size and spleen volume
Slide 7: Mitapivat – an allosteric pyruvate kinase activator
Mitapivat – an allosteric pyruvate kinase activator Glycolytic pathway dysfunction in Mitapivat enhances PK activity and Glucose erythrocyte membranopathies restores glycolytic flux, resulting in: FBP Decreased PK activity and glycolytic flux Increase in ATP levels 1,3-DPG Improved RBC hydration Red
Slide 8: Study design
Study design Setup Locations Sponsor Funding Investigator initiated, Denmark EuroBloodNet Association Agios Pharmaceuticals multicenter, single-arm The Netherlands (Non-profit) phase 2 trial. Sibling study in Canada
Slide 9: Key eligibility criteria
Key eligibility criteria Figure created with biorender.com
Slide 10: Study scheme
Study scheme Figure created with biorender.com
Slide 11: Results
Results W56 analysis set (n=21) !"#$%&'()&*#%**(**(+#,-.#(/'0'1'/'&2# Age, median (range) 44 (24-67) 3#$%&'()&*#4(.(#(56/7+(+# 8#9#+'+#)-&#:((&#(/'0'1'/'&2#6.'&(.'%# 8#;#4'&<+.(4#6-)*()&# Female sex, n (%) 10 (48) !9#$%.&'6'$%)&*#.(6('>(+#:'&%#039;>%&# Diagnosis, n HS 15 =#$%.&'6'$%)&*#+'*6-)&')7(+#&.(
Slide 12: Mitapivat resulted in rapid and sustained hemoglobin improvements
Mitapivat treatment resulted in rapid and sustained hemoglobin improvements Mean difference from baseline during FDP2 1.1 g/dL (95% CI, 0.6 to 1.5, p<0.001) 10/21 (48%) participants achieved a hemoglobin response (≥ 1.0 g/dL) during the fixed-dose period 2 (all with HS) *Error bars represent 95% con
Slide 13: Improvements in reticulocytes and bilirubin
Mitapivat treatment resulted in rapid and sustained improvements in reticulocytes and bilirubin Mean difference W56 Mean difference W56 -81 x109/L (95% CI, -115 to -47, p<0.001) -1.4 mg/dL (95% CI, -2.1 to -0.8, p<0.001)13 *Error bars represent standard deviation
Slide 14: Decrease in serum ferritin concentration
Mitapivat treatment resulted in a decrease in serum ferritin concentration Mean difference W56: 14 -92 µg/L (95% CI, -133 to -51. p=0.001)
Slide 15: Mitapivat improved liver iron concentration in hemoglobin responders
Mitapivat improved liver iron concentration in hemoglobin responders Mean difference -0.44 mg/g dw(95% CI, -0.73 to -0.16, p=0.009) Liver iron concentration (LIC) was calculated using: LIC = 31.94 × (T2*)-1.014
Slide 16: No changes in spleen size and volume were observed
No changes in spleen size and volume were observed 16 Spleen volume was calculated using the standard prolate ellipsoid formula (0.52 x length x width x thickness)
Slide 17: Summary
Summary • In this follow-up analysis, mitapivat treatment resulted in sustained improvements in hemoglobin concentrations and hemolytic markers, most pronounced in patients with HS • Mitapivat led to a decrease in ferritin concentrations, and among patients with a hemoglobin response, a reduction of
Slide 18: Acknowledgments
Acknowledgments University medical Center Utrecht, The Netherlands Sponsor: ERN-EuroBloodNet • Eduard J. van Beers • Pierre Fenaux • Joline L. Saes • Adeline Gladieux • Richard van Wijk • Fatiha Chermat • Evelyn Groot • Minke A.E. Rab • Jonathan R.A. de Wilde • Jennifer Bos Copenhagen University Hos