ArticleBlood red cells & iron2025
Long-term mitapivat treatment is safe and efficacious in patients with sickle cell disease.
Article in Blood red cells & iron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Pilot Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Escalating Multiple Oral Doses of AG-348 in Subjects With Stable Sickle Cell Disease
Evaluation of the Safety,Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
A Phase 2/3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Mitapivat in Subjects With Sickle Cell Disease
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Authors and funding
18 authors.
Funding
Abstract
In a phase 1 open-label study (ClinicalTrials.gov identifier: NCT04000165), mitapivat, a pyruvate kinase (PK) activator that is approved by the US Food and Drug Administration for treating anemia of PK deficiency, showed promise as a disease-modifying therapy for sickle cell disease (SCD). We now report updated findings from a phase 1/2 study with a median follow-up of 132 weeks (2.53 years), involving 15 patients, 13 from the initial study and 2 new to mitapivat. Patients with hemoglobin SS (HbSS) aged ≥18 years started mitapivat 50 mg twice daily for 4 weeks followed by a dose escalation to 100 mg twice daily for another 20 weeks to complete a 24-week core period. Nine patients continued treatment for >120 weeks, resulting in 1884 patient-weeks of exposure to mitapivat. Common treatment-emergent adverse events (TEAEs) included vaso-occlusive crises (VOCs), decreased hormone levels, arthralgia, cough, and COVID-19 infection. Changes in laboratory values were not clinically significant. Serious TEAEs were mainly VOCs in 10 patients, and lung infections in 3; all VOCs were linked to known triggers. No TEAEs led to discontinuation of mitapivat. Of 15 patients, 14 (93%) had at least a 1 g/dL increase in Hb at some point within the 24-week core period, with a mean increase of 1.38 ± 0.88 g/dL. Improvements in Hb, hemolytic markers, oxygen affinity, sickling kinetics, and the ratio of adenosine triphosphate to 2,3-diphosphoglycerate were sustained during the extension period. These findings suggest that long-term mitapivat is safe and effective for patients with SCD, warranting further investigation in the ongoing phase 3 study (RISE UP; ClinicalTrials.gov identifier: NCT05031780). This trial was registered at www.ClinicalTrials.gov as #NCT04610866.
Identifiers
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Registered trials
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