Agios' Phase 3 ACTIVATE-Kids Study of Mitapivat in Non-Transfused Children with PK Deficiency Met Primary Endpoint

Agios Pharmaceuticals, Inc., a leader in cellular metabolism therapies for rare diseases, has announced significant results from its ACTIVATE-Kids Phase 3 study. This study focused on the efficacy of mitapivat in children aged 1 to under 18 years who suffer from pyruvate kinase (PK) deficiency and are not regularly receiving transfusions. The trial successfully met its primary goal, showing a marked response in hemoglobin levels.

During the 20-week double-blind period of the ACTIVATE-Kids study, safety outcomes aligned with previously recorded safety data from adult patients with the same condition. A parallel Phase 3 study, known as ACTIVATE-KidsT, explored the effects of mitapivat in children who do receive regular transfusions, with initial results reported in August 2024.

Dr. Sarah Gheuens, Chief Medical Officer at Agios, noted that the positive outcomes of the ACTIVATE-Kids trial signify a pivotal moment for those affected by PK deficiency. The findings build upon prior evidence of mitapivat's benefits in adults and form a foundation for future pediatric studies involving other conditions like thalassemia and sickle cell disease. Dr. Gheuens expressed gratitude to the trial participants and their families for their contributions.

In the ACTIVATE-Kids trial, 30 children were part of the study, with 19 receiving mitapivat twice daily and 11 on a placebo. The study's primary endpoint was a hemoglobin response, defined as an increase of 1.5 g/dL or more in hemoglobin concentration from baseline, sustained over multiple assessments during the trial. The analysis, which leaned on Bayesian statistical methods and data from related adult studies, confirmed the desired outcome across all predetermined statistical measures. Specifically, 31.6% of those on mitapivat achieved the hemoglobin response, compared to none in the placebo group, with a significant confidence interval supporting these results.

Additionally, patients on mitapivat showed improvements in biomarkers of hemolysis, such as indirect bilirubin and lactate dehydrogenase, compared to those on placebo. All participants completed the study's 20-week period, and adverse event rates were comparable between the mitapivat and placebo groups, with no treatment discontinuations.

Dr. Rachael F. Grace from the Dana-Farber/Boston Children’s Cancer and Blood Disorder Center highlighted the impact of PK deficiency, which can severely disrupt a child's life with fatigue and serious complications. She emphasized the potential of mitapivat to offer meaningful clinical benefits, such as improved anemia management and reduced transfusion needs, for children with PK deficiency.

Following the promising outcomes from the ACTIVATE-Kids and ACTIVATE-KidsT studies, Agios plans to submit a marketing application to offer mitapivat as a treatment for pediatric patients with PK deficiency. The company also intends to present further detailed analyses from these studies at upcoming medical conferences.

Agios has positioned itself at the forefront of PK activation research, developing transformative treatments for rare diseases. In the United States, the company has already introduced a pioneering pyruvate kinase activator for adults with PK deficiency—marking a significant advancement in managing this lifelong and debilitating condition. Building on its expertise, Agios is advancing a diverse clinical pipeline targeting conditions like thalassemia, sickle cell disease, and myelodysplastic syndrome-associated anemia.