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Vol. 46. Núm. S4.
HEMO 2024
Páginas S34-S35 (outubro 2024)
Vol. 46. Núm. S4.
HEMO 2024
Páginas S34-S35 (outubro 2024)
Acesso de texto completo
IMPROVEMENTS IN FATIGUE AND 6-MINUTE WALK TEST IN ADULTS WITH ALPHA- OR BETA-NON–TRANSFUSION-DEPENDENT THALASSEMIA: THE PHASE 3 ENERGIZE TRIAL OF MITAPIVAT
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KH Kuoa, H Al-Samkarib, Y Aydinokc, M Besserd, S Gheuense, G Lunaf, A Glenthjg, AS Gohh, A Kattamisi, SR Loggettoj, KM Musallamk, P Ricchil, E Salido-Fiérrezm, S Shethn, V Viprakasito, MD Cappellinip, AT Taherq
a Division of Hematology, University of Toronto, Toronto, Canada
b Division of Hematology and Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, United States
c Department of Paediatric Haematology and Oncology, Ege University School of Medicine, Izmir, Turkey
d Department of Haematology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
e Agios Pharmaceuticals, Inc., Cambridge, United States
f Centre de Référence Syndromes Drépanocytaires Majeurs, Thalassémies et Autres Pathologies Rares du Globule Rouge et de l’Érythropoïèse, Hôpital Henri Mondor APHP, Paris, France
g Department of Haematology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
h Haematology Unit, Department of Medicine, Hospital Pulau Pinang, Penang, Malaysia
i Thalassemia Unit, First Department of Pediatrics, National and Kapodistrian University of Athens, Athens, Greece
j São Paulo Blood Bank – GSH Group, São Paulo, Brazil
k Center for Research on Rare Blood Disorders (CR-RBD), Burjeel Medical City, Abu Dhabi, UAE
l Unità Operativa Semplice Dipartimentale Malattie Rare del Globulo Rosso, Azienda Ospedaliera di Rilievo, Napoli, Italy
m Department of Haematology, Hospital Clínico Universitario Virgen de la Arrixaca-IMIB, Murcia, Spain
n Division of Hematology and Oncology, Department of Pediatrics, Weill Cornell Medicine, New York, United States
o Department of Pediatrics & Thalassemia Center, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
p Department of Clinical Sciences and Community, University of Milan, Ca'Granda Foundation IRCCS Maggiore Policlinico Hospital, Milan, Italy
q Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
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Vol. 46. Núm S4

HEMO 2024

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Background

Thalassemia, a group of inherited disorders characterized by ineffective erythropoiesis and chronic hemolytic anemia, is associated with wide-ranging impacts on health-related quality of life (HRQoL), such as impaired physical functioning and fatigue. Anemia has been associated with increased symptom burden and poor HRQoL in patients (pts) with non–transfusion-dependent thalassemia (NTDT). There are no available oral disease-modifying therapies that have been shown to improve HRQoL in β-thalassemia and no agents are approved for α-thalassemia. In a phase 2 study of pts with NTDT, improvements in hemoglobin were observed with mitapivat, a first-in-class, oral, allosteric activator of pyruvate kinase, and it has the potential to improve HRQoL.

Aims

To evaluate the impact of mitapivat vs placebo on fatigue, physical function, and other thalassemia symptoms in adults with α- or β-NTDT in ENERGIZE, a phase 3, double-blind, randomized, placebo-controlled, global trial.

Methods

Adults (≥18 years) were randomized 2:1 to mitapivat 100 mg twice daily or placebo for 24 weeks (wks). NTDT was defined as ≤5 red blood cell (RBC) units transfused in the 24 wks before randomization and no RBC transfusions ≤8 wks before informed consent or during screening. The Functional Assessment of Chronic Illness Therapy–Fatigue Scale (FACIT-Fatigue), 6-Minute Walk Test (6MWT), and Patient Global Impression of Change (PGIC) of Fatigue, Thalassemia Symptoms, and Walking Capacity were among the outcomes assessed. Changes from baseline (BL) for FACIT-Fatigue (Wks 12–24) and 6MWT (Wk 24), and the results of PGIC-Fatigue, (Wks 12–24), PGIC-Thalassemia Symptoms, and PGIC-Walking Capacity (both Wk 24) were summarized. The clinically meaningful within-person change (MWPC) threshold for FACIT-Fatigue was estimated to be a ≥4.5-point change from BL in average score from Wks 12–24, using an anchor-based method.

Results

194 pts were randomized (mitapivat n = 130; placebo n = 64); BL characteristics were similar between treatment arms. Mitapivat demonstrated a statistically significant improvement compared with placebo in change from BL to Wk 12–24 average FACIT-Fatigue score; least-squares mean (LSM) change from BL was 4.85 for mitapivat vs 1.46 for placebo (LSM difference (95% CI): 3.40 (1.21, 5.59); 2-sided p < 0.0026), and 36.2% of pts in the mitapivat arm achieved the MWPC threshold of ≥4.5 vs 21.9% in the placebo arm. For the 6MWT, LSM change from BL to Wk 24 was 30.48 m for mitapivat and 7.11 m for placebo (LSM difference (95% CI): 23.36 m (6.90, 39.83)). The observed frequency of pts with improvements (reporting feeling much/a little better) in PGIC-Fatigue was higher for pts in the mitapivat arm than the placebo arm at Wk 12 (63.1% vs 23.4%), Wk 16 (69.2% vs 23.4%), Wk 20 (62.3% vs 28.1%), and Wk 24 (60.8% vs 31.3%). Improvements in PGIC-Thalassemia Symptoms and PGIC-Walking Capacity were also reported in a higher frequency of pts in the mitapivat arm than in the placebo arm at Wk 24 (67.7% vs 32.8%; 55.4% vs 28.1%, respectively).

Summary/Conclusion

Mitapivat is the first oral, disease-modifying, investigational therapy with which meaningful improvements in aspects of HRQoL, including fatigue and walking capacity, were observed in a clinical trial that enrolled both pts with α-NTDT and pts with β-NTDT.

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Idiomas
Hematology, Transfusion and Cell Therapy
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