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Mitapivat, a first\u2010in\u2010class, oral, small\u2010molecule allosteric activator of red blood cell pyruvate kinase, is under investigation in adults with thalassaemia. Through its mechanism of action, mitapivat increases adenosine triphosphate, leading to improvements in red blood cell health, ineffective erythropoiesis and haemolysis. An open\u2010label, multicentre, phase 2 study (NCT03692052) is evaluating mitapivat 100\u2009mg twice daily in adults with NTDT. We previously reported a statistically significant haemoglobin response (a \u22651.0\u2009g\/dL increase in haemoglobin concentration from baseline at \u22651 assessments between Weeks 4 and 12 [inclusive]) during the 24\u2010week core period. Here, we report efficacy and safety results up to Week 156 and to data cut\u2010off date respectively. Of 20 patients enrolled, 17 continued in the extension period. Median change from baseline in haemoglobin concentration at Week 156 was 1.2\u2009g\/dL. Patients receiving mitapivat demonstrated sustained improvements in haemoglobin concentrations and markers of erythropoietic activity, haemolysis and iron homeostasis. Five patients (29%) had a grade \u22653 treatment\u2010emergent 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.<\/jats:p>","DOI":"10.1111\/bjh.20058","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T01:58:42Z","timestamp":1747792722000},"page":"1764-1773","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Long\u2010term efficacy and safety of mitapivat in non\u2010transfusion\u2010dependent \u03b1\u2010 or \u03b2\u2010thalassaemia: An open\u2010label phase 2 study"],"prefix":"10.1111","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6744-9238","authenticated-orcid":false,"given":"Kevin H. 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