The trial also demonstrated reductions in indirect bilirubin, lactate dehydrogenase, and haptoglobin levels in mitapivat-treated patients. How do these biomarker changes correlate with disease severity and symptom relief in children with PK deficiency?

Mitapivat was well tolerated in the trial, with adverse event rates comparable to placebo and no treatment discontinuations. Given that this is the first oral therapy tested in this population, what are the key safety considerations for long-term use in children?

As a pyruvate kinase activator, mitapivat directly enhances red blood cell energy metabolism. How does this mechanism compare to traditional supportive care, and what potential does it have beyond PK deficiency, such as in sickle cell disease or thalassemia?

With positive Phase 3 data from both ACTIVATE-Kids and ACTIVATE-KidsT, Agios plans to submit a marketing application for mitapivat in pediatric PK deficiency. What are the key regulatory considerations for pediatric rare disease approvals, and how might this impact access to treatment?

Since PK deficiency can lead to chronic anemia, fatigue, and complications over time, what additional long-term data would be needed to determine if mitapivat provides a disease-modifying effect rather than just symptomatic relief?

Currently, treatment options for PK deficiency are limited to transfusions or splenectomy in severe cases. How does mitapivat compare to these interventions, and do you see it becoming a first-line therapy for pediatric patients?

Beyond PK deficiency, mitapivat is being studied in sickle cell disease and thalassemia. What lessons from the ACTIVATE-Kids study could inform future trials, and how promising is mitapivat’s potential in these broader indications?