Mitapivat improves Hb levels in paediatric patients with PK deficiency

Treatment with mitapivat increased haemoglobin (Hb) levels in children with pyruvate kinase (PK) deficiency who were not receiving regular blood transfusions, according to the ACTIVATE-Kids trial presented at ASH 2025.

This phase III, global, multicentre, double-blind, placebo-controlled study analysed 30 children (mean age 9.6 years) who were not regularly transfused (defined as ≤5 transfusions in the 52-week period before providing informed consent/assent and no RBC transfusions within 12 weeks of the first dose of the study drug). Participants were randomized in a 2:1 ratio to receive either oral mitapivat (1–5 mg based on age and weight, with potential escalation up to 10–50 mg) twice daily (n=19) or placebo (n=11) for 20 weeks. Mean baseline Hb levels were 8.48 and 8.46 g/dL, respectively.

From weeks 12 to 20, 31.6 percent of patients treated with mitapivat achieved an Hb response, defined as an increase in Hb concentration of ≥1.5 g/dL from baseline, sustained at ≥2 scheduled assessments at weeks 12, 16, and 20. In contrast, none of those treated with placebo achieved this response. [ASH 2025, P4654]

“The primary endpoint of the study was met; the observed Hb response rate was higher for patients in the mitapivat arm than in the placebo arm,” said Dr Satheesh Chonat from Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta in Atlanta, Georgia, US.

With regard to secondary endpoints, mitapivat treatment improved Hb concentration compared with placebo from week 12 through week 20 (least squares mean difference from baseline, 0.90 g/dL).

Patients treated with mitapivat also experienced improvements in markers of haemolysis, as shown by a greater reduction in indirect bilirubin (-43.06 vs -15.81 µmol/L) and lactate dehydrogenase (-94.41 vs 59.67 U/L) over time compared with placebo.

Additionally, more mitapivat-treated patients did not require any on-study transfusions than placebo-treated patients (78.9 percent vs 45.5 percent).

As for safety, treatment-emergent adverse events (TEAEs) occurred in 78.9 percent of patients in the mitapivat group vs 90.9 percent in the placebo group.

One patient in each group experienced serious TEAEs, specifically bronchitis and asthma in the mitapivat group and a viral respiratory infection in the placebo group. However, none of these events was deemed treatment-related.

The most common TEAEs reported with mitapivat were upper respiratory infection (26.3 percent), headache (15.8 percent), and initial insomnia (15.8 percent).

Mitapivat was generally well tolerated, with a consistent safety profile observed in adults and regularly transfused children with PK deficiency, said Chonat.

Overall, "the efficacy and safety results from the ACTIVATE-Kids study support the potential for mitapivat to provide clinically substantial benefits in children with PK deficiency," Chonat conlcuded.