Long‐term efficacy and safety of mitapivat in non‐transfusion‐dependent α‐ or β‐thalassaemia: An open‐label phase 2 study
Bibliographic record
Abstract
Non-transfusion-dependent thalassaemia (NTDT) can result in serious complications and comorbidities that can impact patients' quality of life. Mitapivat, a first-in-class, oral, small-molecule 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-label, multicentre, phase 2 study (NCT03692052) is evaluating mitapivat 100 mg twice daily in adults with NTDT. We previously reported a statistically significant haemoglobin response (a ≥1.0 g/dL increase in haemoglobin concentration from baseline at ≥1 assessments between Weeks 4 and 12 [inclusive]) during the 24-week core period. Here, we report efficacy and safety results up to Week 156 and to data cut-off 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 g/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 ≥3 treatment-emergent 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".