Following its recent US FDA approval, on this episode, Pip and Rich discuss mitapivat, an allosteric activator of red-cell pyruvate kinase. They focus on ENERGIZE, a randomised controlled trial of mitapivat vs placebo (2:1) randomisation in people living with transfusion dependent thalassaemia. It met its primary endpoint of achieving significantly more patients reaching a haemoglobin rise of at least 1 g/L. However, Pip and Rich discuss the relevance of this surrogate endpoint as well as the small effects on fatigue and quality of life.