Efficacy and safety of mitapivat in adults with transfusion-dependent α-thalassaemia or β-thalassaemia (ENERGIZE-T): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial.

What was studied

ENERGIZE-T was a global phase 3 trial. It was double-blind and placebo-controlled. It ran in 19 countries. Patients were aged 18 years or older. They had transfusion-dependent α-thalassaemia or β-thalassaemia. Mitapivat is an oral activator of pyruvate kinase. 258 patients were assigned by chance, 2 to 1. Doses were 100 mg of mitapivat or placebo. They were taken by mouth 2 times a day. Treatment lasted 48 weeks. The main goal was transfusion reduction response (TRR). TRR meant a cut of at least 50 per 100 in red cell units transfused. It also needed a drop of at least 2 units. This held in any 12-week period up to week 48.

What they found

TRR occurred in 52 of 171 patients on mitapivat, or 30 per 100. On placebo it was 11 of 87, or 13 per 100. The adjusted gap was 18 points. The range was 8 to 27. The p value was 0·0003. 238 of 258 patients completed the double-blind period. Adverse events occurred in 155 of 172 on mitapivat, or 90 per 100. They occurred in 71 of 85 on placebo, or 84 per 100. Headache, upper respiratory infection, insomnia, diarrhoea and fatigue were most common with mitapivat. Serious adverse events occurred in 19 on mitapivat, or 11 per 100. They occurred in 13 on placebo, or 15 per 100. Adverse events led 6 per 100 on mitapivat to stop treatment. On placebo it was 1 per 100. No deaths were reported.

What it means for patients

The authors say mitapivat significantly reduced the transfusion burden. They say it was generally well tolerated, with a favourable benefit-risk profile. They say the findings support mitapivat as an oral therapy that modifies the disease. This is for adults who depend on transfusions for thalassaemia.

Why it is not certain yet

Adverse events were more frequent with mitapivat, at 90 per 100 versus 84 per 100. The trial was funded by Agios Pharmaceuticals. The abstract gives no other limits. A single trial can only show so much.

Source

Efficacy and safety of mitapivat in adults with transfusion-dependent α-thalassaemia or β-thalassaemia (ENERGIZE-T): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial.

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