In a groundbreaking development for rare blood disorder treatment, Agios Pharmaceuticals announced that its Phase 3 ACTIVATE-Kids study of mitapivat achieved its primary endpoint in children with pyruvate kinase (PK) deficiency who are not regularly transfused. The trial marks a significant milestone as the first demonstration of an oral therapy's efficacy in pediatric PK deficiency patients.
The multicenter study enrolled 30 patients aged 1 to under 18 years, with 19 receiving mitapivat twice daily and 11 receiving placebo. The trial's success was measured by hemoglobin response, defined as a ≥1.5 g/dL increase in hemoglobin concentration sustained at multiple assessments during weeks 12, 16, and 20 of the double-blind period.
Clinical Efficacy and Safety Outcomes
The study demonstrated compelling efficacy, with 31.6% (6/19) of patients in the mitapivat arm achieving hemoglobin response compared to no responses in the placebo group. The difference was statistically significant, with a 95% confidence interval of 10.8% to 52.7%. Additionally, patients receiving mitapivat showed improvements in key markers of hemolysis, including indirect bilirubin, lactate dehydrogenase, and haptoglobin levels.
Safety results aligned with the previously established profile in adult patients. Both treatment arms showed comparable adverse event rates, with no discontinuations due to adverse events during the 20-week double-blind period.
Expert Perspectives
"The positive results for the ACTIVATE-Kids Phase 3 trial represent a very important step forward for the PK deficiency community," stated Dr. Sarah Gheuens, Chief Medical Officer and Head of R&D at Agios. She emphasized the significance of these findings in shaping future pediatric clinical programs for thalassemia and sickle cell disease.
Dr. Rachael F. Grace from Dana-Farber/Boston Children's Cancer and Blood Disorder Center highlighted the impact on patient quality of life: "PK deficiency can lead to debilitating fatigue and a range of serious complications and symptoms, severely affecting and disrupting a child's quality of life."
Clinical Program Expansion
The ACTIVATE-Kids trial is part of Agios' broader pediatric clinical program for rare hemolytic anemias. In August 2024, the company reported positive topline results from the companion ACTIVATE-KidsT Phase 3 study, which evaluated mitapivat in regularly transfused children with PK deficiency.
Regulatory Path Forward
Based on the positive outcomes from both ACTIVATE-Kids and ACTIVATE-KidsT studies, Agios plans to submit a marketing application for mitapivat in pediatric patients with PK deficiency. The company will present detailed analyses from both studies at upcoming medical conferences.
Treatment Implications
For children with PK deficiency, mitapivat represents a potential breakthrough in disease management. The drug's ability to improve anemia and reduce transfusion requirements could significantly impact the standard of care for this rare genetic disorder. Currently, PYRUKYND® (mitapivat) is approved for adult patients with PK deficiency in the United States, with specific safety considerations including monitoring for acute hemolysis upon discontinuation and potential hepatocellular injury.
