ASH 2024 | ENERGIZE-T: a Phase III study of mitapivat in transfusion-dependent alpha- or beta-thalassemia

ENERGIZE-T is a phase 3 open-label double-blind control study of mitapivat in transfusion-dependent thalassemia patients. Patients were randomized to mitapivat and placebo, two mitapivat and one placebo. The dosage of mitapivat was 100 milligrams twice a day, is an oral compound and the double-blind period was 48 weeks. After 48 weeks the patients in placebo could switch to mitapivat for another long-term follow-up study for five years. 

So I’ll just mention the aim of the study and then I move to the results. The primary endpoint was the reduction of equal or more than 50% of transfusion burden compared to baseline. And then we had three other secondary endpoints which were looking respectively at a decline of equal or more than 50 percent or a decline of equal or more than 33 percent in different periods. The primary endpoint was the decline, the reduction at any 12 week. For the secondary endpoint, the reduction was at any 24 weeks or in a well-defined period from week 13 to the end of the study. 

The results were very positive because the primary endpoint was met with a statistically significant difference between mitapivat-treated patients and placebo as well as for the secondary endpoint. All met the endpoint. In terms of safety, I have to say that I have no specific concern because it is a drug which is modulating the red cell metabolism. So it’s an activator of PK and with the activation of PK there is an increase of the glycolytic pathway with an increased production of ATP and increased production of energy. So this is the main mechanism of mitapivat which is going to improve the survival of the thalassemic red cells. And as I say, in terms of safety, there were no adverse events attributable to the drug. Most were comparable between the mitapivat arm and placebo arm and were quite common adverse events, which we are used to seeing in thalassemia patients. Let’s say that in the mitapivat group we observe, at least at the beginning of the treatment, some patients who experience insomnia, fatigue, but all these were transient and manageable side effects. 

So at the end of the day the results are quite positive, supporting hopefully the approval of mitapivat, but not only for the transfusion-dependent thalassemia patients, but just recently the data on non-transfusion dependent have been also published.

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