Agios Reports Positive Results from Phase 3 Mitapivat Study in NTD Thalassemia

Rare Daily Staff

Agios Pharmaceuticals presented detailed positive results from the global phase 3 ENERGIZE study of its oral therapy mitapivat in adults with non-transfusion-dependent alpha- or beta-thalassemia showing the study achieved its primary endpoint.

The results, presented in a plenary session at the European Hematology Association 2024 Hybrid Congress in Madrid, Spain showed statistical significance was also achieved for both key secondary endpoints associated with change from baseline in FACIT-Fatigue Score and hemoglobin concentration. These improvements were observed across all pre-specified subgroups. Additionally, the study found clinically meaningful improvements in health-related quality of life measures and patient-reported outcomes among patients in the mitapivat arm compared to those in the placebo arm.

Thalassemia is a genetic blood disorder that prevents the body from producing adequate amounts hemoglobin, a protein in red blood cells that deliver oxygen to cells throughout the body. People with non-transfusion dependent thalassemia do not require regular transfusions throughout their lives to survive.

Mitapivat is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency in the United States, and for the treatment of PK deficiency in adult patients in the European Union.

The company intends to file for regulatory approval of mitapivat as a treatment for thalassemia by the end of 2024, incorporating all available data from both studies.

The study met the primary endpoint of hemoglobin response. Hemoglobin response was defined as an increase of ≥1 g/dL in average hemoglobin concentrations from week 12 through week 24 compared with baseline.

Some 42.3 percent of patients in the mitapivat arm achieved a hemoglobin response, compared to 1.6 percent of patients in the placebo arm.

Improvements were observed in patients treated with mitapivat across measures of health-related quality-of-life, including the six-minute walk test and the Patient Global Impression of Change (PGIC) fatigue, walking capacity, and thalassemia symptoms subscales.

Overall, during the 24-week double-blind period, incidence of adverse events was similar across mitapivat and placebo arms, with 82.9 percent of patients in the mitapivat arm and 79.4 percent of patients in the placebo arm experiencing treatment-emergent adverse events. The most frequently reported TEAEs were headache, initial insomnia, nausea and upper respiratory tract infection.

“The data from the ENERGIZE study are compelling, with mitapivat-treated patients achieving meaningful improvements in non-transfusion-dependent thalassemia’s hallmark symptom of anemia as well as in key measures of how patients feel and function,” said Sarah Gheuens, chief medical officer and head of R&D at Agios. “Together with the recently announced positive results from the ENERGIZE-T study of mitapivat in adults with transfusion-dependent thalassemia, the detailed ENERGIZE results underscore mitapivat’s potential to become an important treatment option for all subtypes of thalassemia – alpha- and beta-thalassemia, transfusion-dependent and non-transfusion-dependent – with the convenience of a pill.”

Photo: Sarah Gheuens, chief medical officer and head of R&D at Agios