Agios Announces Phase 3 ACTIVATE-KidsT Study Results of Mitapivat in Regularly Transfused Children with PK Deficiency

Agios Pharmaceuticals, Inc., a renowned entity in cellular metabolism and pyruvate kinase (PK) activation, recently disclosed topline results from its global Phase 3 ACTIVATE-KidsT study. This study evaluated mitapivat in children aged 1 to 18 years with PK deficiency who are regularly transfused. Despite not meeting the prespecified statistical criterion for the primary endpoint using Bayesian methodology, the results were clinically significant.

In the ACTIVATE-KidsT study, the primary endpoint was transfusion reduction response (TRR), and 28.1% of patients in the mitapivat group achieved this endpoint compared to 11.8% in the placebo group. Furthermore, secondary endpoints such as transfusion-free response and normal hemoglobin response were only observed in patients treated with mitapivat. Specifically, 18.8% of patients in the mitapivat arm experienced a transfusion-free response, and 12.5% achieved normal hemoglobin levels.

During the 32-week double-blind treatment period, mitapivat was considered generally safe and well-tolerated. The safety profile of mitapivat aligned with previous observations in adults with PK deficiency who undergo regular transfusions. No patients discontinued the study due to adverse events.

Sarah Gheuens, M.D., Ph.D., Chief Medical Officer and head of R&D at Agios, expressed satisfaction with the results, highlighting the potential of mitapivat as the first-ever pediatric treatment for PK deficiency. She emphasized the significance of these findings for children and their caregivers, who currently have no disease-modifying therapies. The company anticipates completing the pediatric PK deficiency clinical development program next year with the readout of the ACTIVATE-Kids study, which involves children who are not regularly transfused.

Dr. Rachael F. Grace, an investigator in the ACTIVATE-KidsT study from the Dana-Farber/Boston Children’s Cancer and Blood Disorder Center, underscored the substantial burden of PK deficiency on children. Symptoms such as fatigue, the need for blood transfusions, and the risk of iron overload can disrupt regular childhood activities. The ACTIVATE-KidsT trial is the first of its kind to demonstrate the potential for mitapivat to offer meaningful clinical benefits in children, including anemia resolution and reduced need for transfusions.

Agios has also completed enrollment for the Phase 3 ACTIVATE-Kids study, focusing on children with PK deficiency who are not regularly transfused, with topline data expected in 2025. The ACTIVATE-KidsT trial enrolled 49 patients, with 32 receiving mitapivat and 17 receiving a placebo. The trial results showed that a higher percentage of patients in the mitapivat arm achieved the primary and secondary endpoints compared to the placebo arm.

In summary, the Phase 3 ACTIVATE-KidsT study revealed promising clinical benefits of mitapivat in children with PK deficiency who are regularly transfused. The drug was well-tolerated and showed a safety profile consistent with previous studies in adults. Agios plans to present a detailed analysis of the Phase 3 data at an upcoming medical meeting, as they continue to advance their clinical pipeline targeting rare hemolytic anemias.