Efficacy and safety of mitapivat in patients with sickle cell disease (RISE UP): a phase 3, double-blind, global, randomised, placebo-controlled trial.

What was studied

RISE UP was a phase 3 trial of mitapivat in sickle cell disease. It was double-blind and placebo-controlled. It ran at 69 sites in 15 countries. Mitapivat is an oral drug that activates pyruvate kinase. The team aimed to test its efficacy and safety. Patients were older than 16 years. They had anaemia and repeated sickle cell pain crises. They were assigned by chance, 2 to 1, to mitapivat 100 mg or placebo. The dose was taken 2 times a day. The main goals were haemoglobin response and the yearly rate of pain crises. Response meant a rise of 1·0 g/dL in average haemoglobin. This was measured from week 24 to week 52.

What they found

207 patients were assigned. 138 got mitapivat and 69 got placebo. A haemoglobin response occurred in 56 of 138 on mitapivat, or 41 per 100. On placebo it was 2 of 69, or 3 per 100. The adjusted gap was 38 per 100, with a range of 29 to 47. The p value was below 0·0001. The yearly pain crisis rate was 2·6 with mitapivat. It was 3·1 with placebo. The p value was 0·1213. Serious adverse events occurred in 28 of 138 on mitapivat, or 20 per 100. They occurred in 20 of 69 on placebo, or 29 per 100. 1 patient on mitapivat and 0 on placebo had an event judged treatment related.

What it means for patients

The authors say mitapivat activates pyruvate kinase by a novel mechanism. They say it eases haemolytic anaemia. They say it could become an effective, convenient treatment that modifies the disease.

Why it is not certain yet

Pain crises did not differ significantly between groups. The p value was 0·1213. The trial was funded by Agios Pharmaceuticals. A single trial can only show so much.

Source

Efficacy and safety of mitapivat in patients with sickle cell disease (RISE UP): a phase 3, double-blind, global, randomised, placebo-controlled trial.

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