Agios’ first-ever pediatric data readout missed the primary endpoint, with its drug Pyrukynd (mitapivat) not showing statistical significance in children with pyruvate kinase (PK) deficiency who are regularly transfused.
But the biotech said the Phase 3 trial also carries positive takeaways, including a consistent safety profile and “clinically meaningful” results on both the primary and secondary endpoints.
In the Phase 3 trial, 28.1% of patients taking Pyrukynd saw a transfusion reduction response, compared to 11.8% of patients in the placebo arm, failing to meet the prespecified statistical criterion on the primary endpoint.
On the secondary endpoints — transfusion-free response and normal hemoglobin response — Agios said the drug showed an effect, with 18.8% of patients on the drug seeing a transfusion-free response and 12.5% hitting normal hemoglobin levels, compared to none in the placebo group.
As for safety, the drug was well-tolerated, according to Agios, and consistent with the safety profile for adults with PK deficiency who are regularly transfused. More data will be shared at an upcoming medical meeting.
Despite the primary endpoint miss, Agios CMO and head of R&D Sarah Gheuens wrote in a statement that “it is gratifying to share encouraging efficacy and safety data that may support the potential of a first-ever pediatric treatment for this rare blood disorder.”
Leerink Partners analysts were also hopeful, writing Thursday that “importantly, the safety results were consistent with the safety profile seen in adult patients, which may be more relevant to the larger, pending indications like sickle-cell disease.”
The analysts added that the data suggest a clinical benefit to children with the disease, “although the lack of a [statistical significant] result increases regulatory uncertainty, or suggests the potential for a limited label.”
Pyrukynd, which is already approved in the US for hemolytic anemia in adults with PK deficiency, is also being studied in children with PK deficiency who are not regularly transfused. Topline data are expected next year.
The drug is also being investigated in a number of other indications, including non-transfusion dependent adult thalassemia, transfusion-dependent adult thalassemia and sickle cell disease.
Earlier this year, Agios executives said they planned to file for US approval by the end of 2024 for Pyrukynd in transfusion-dependent thalassemia patients following a positive data readout. Of the patients who received Agios’ drug in the trial, 30% achieved a transfusion reduction response, compared to 13% of patients on placebo.