RARE Daily

Agios Reports Phase 3 Beta-Thalassemia Study Met All Primary Endpoints

June 3, 2024

Rare Daily Staff

Agios Pharmaceuticals said that the global phase 3 ENERGIZE-T study of mitapivat in adults with the rare blood disorder transfusion-dependent alpha- or beta-thalassemia achieved its primary endpoint of transfusion reduction response.

Statistical significance was also achieved for all key secondary endpoints evaluating additional measures of reduction of transfusion burden compared to placebo.

Transfusion-dependent beta thalassemia (TDT) is a serious, life-threatening genetic disease. TDT requires frequent blood transfusions and iron chelation therapy throughout a person’s life. Due to anemia, patients living with TDT may experience fatigue and shortness of breath, and infants may develop failure to thrive, jaundice and feeding problems. Complications of TDT can also include an enlarged spleen, liver and/or heart, misshapen bones, and delayed puberty. TDT requires lifelong treatment and significant use of health care resources, and ultimately results in reduced life expectancy, decreased quality of life, and reduced lifetime earnings and productivity. In the U.S., the median age of death for patients living with TDT is 37 years. Stem cell transplant from a matched donor is a curative option but is only available to a small fraction of people living with TDT because of the lack of available donors.

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

“Taken together with the positive data from the ENERGIZE study, the data from the ENERGIZE-T study have the potential to be transformative for thalassemia patient care. Treatment options for patients with transfusion-dependent thalassemia are limited, and transfusions carry significant risks for patients, such as iron overload and immune reactions. There is a tremendous need for alternative ways to manage this chronic disease,” said Maria Domenica Cappellini, professor, Internal Medicine, University of Milan, Italy. “Based on these data demonstrating that treatment with mitapivat significantly reduces transfusion burden across alpha- and beta-thalassemia patients, along with its convenient oral formulation, mitapivat has the potential to become a novel advancement in care for thalassemia patients.”

A total of 258 patients were enrolled in the study, with 171 randomized to mitapivat 100 mg twice daily and 87 randomized to matched placebo. A total of 155 patients (90.6 percent) in the mitapivat arm and 83 patients (95.4 percent) in the placebo arm completed the 48-week double-blind period of the study.

The study met its primary endpoint of transfusion reduction response. Treatment with mitapivat demonstrated a statistically significant reduction in transfusion burden compared to placebo, as measured by the TRR endpoint. In the mitapivat arm, 30.4 percent of patients achieved a transfusion reduction response, compared to 12.6 percent of patients in the placebo arm.

Treatment with mitapivat also demonstrated a statistically significant reduction in additional measures of transfusion reduction response compared to placebo as assessed by the three key secondary endpoints.

Overall, during the 48-week double-blind period, incidence of adverse events was similar across mitapivat and placebo arms. In the mitapivat arm, 5.8 percent of the patients experienced an adverse event leading to discontinuation, compared to 1.2 percent of patients in the placebo arm.

Based on the safety and efficacy data observed in ENERGIZE-T, the company will proceed with the previously stated plans of U.S. regulatory submission by end of this year. The company also plans to submit marketing applications in Europe and the Gulf Cooperation Council countries.


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