Agios Pharmaceuticals reported new data further underscoring the significant burden of disease in adults with pyruvate kinase (PK) deficiency regardless of genotype and supporting the potential benefits of treatment with PYRUKYND® for these patients.
Data were presented at the European Hematology Association (EHA) Annual Congress, hosted virtually and in person in Vienna on June 9-12, 2022.
“Following the FDA approval of PYRUKYND® for the treatment of hemolytic anemia in adults with PK deficiency in February of this year, the data presented at EHA add to the growing body of evidence underscoring the potential of PYRUKYND® to provide real-world benefits for patients with this rare blood disorder,” said Sarah Gheuens, M.D., Ph.D., chief medical officer at Agios. “Patients treated with PYRUKYND® had early and robust hemoglobin responses and improvements in hallmark signs and symptoms of PK deficiency, including jaundice, tiredness, and shortness of breath. In addition, new data from the Peak Registry highlight the importance of appropriate disease management for all patients with PK deficiency, regardless of genotype. Agios continues to focus on maximizing the impact of PYRUKYND® as the first approved disease-modifying treatment for this community.”
PYRUKYND® was approved in February 2022 by the U.S. Food and Drug Administration (FDA) for the treatment of hemolytic anemia in adults with PK deficiency. PYRUKYND® is also under review by the European Medicines Agency (EMA) as a potential treatment for adults with PK deficiency, and Agios expects a regulatory decision in the EU by the end of 2022.
Long-term Treatment with Mitapivat Associated with Normalization of Hemoglobin Levels in Patients with PKD
This analysis of data from the Phase 3 ACTIVATE study and the ongoing long-term extension study assessed the proportion of patients who achieved normal hemoglobin levels, as defined by central and local laboratory manuals, at least once while receiving PYRUKYND® without requiring any transfusions. Data demonstrate that treatment with PYRUKYND® was associated with normalization of hemoglobin levels. A greater proportion of patients achieved normalization of hemoglobin levels among the subset who met the primary endpoint as hemoglobin responders, defined as a hemoglobin increase of ≥1.5 g/dL at ≥2 scheduled assessments at weeks 16, 20, and 24 during the fixed-dose period.
As of the September 21, 2021 data cut-off, 40/40 patients in the mitapivat arm and 38/40 patients in the placebo crossover arm continued treatment in the extension study. Results were as follows:
- Across the ACTIVATE and extension studies, 28/78 (35.9%) of all patients achieved a normal hemoglobin level at least once during treatment with PYRUKYND®
- Among hemoglobin endpoint responders, 26/31 (83.9%) achieved a normal hemoglobin level at least once while receiving treatment with mitapivat
- The majority of patients who achieved a normal hemoglobin level at least once in the ACTIVATE and extension studies achieved their first normal hemoglobin level within four months of treatment with PYRUKYND®
Improvements in Patient-Reported Outcomes in Mitapivat-treated Patients with Pyruvate Kinase Deficiency: A Descriptive Analysis from the Phase 3 ACTIVATE Trial
The purpose of this post-hoc analysis of the ACTIVATE Phase 3 study was to describe the changes in patient-reported outcomes (PROs) for the subset of patients who achieved the primary endpoint of hemoglobin response. Measurements were taken using two disease-specific PRO instruments: the PK deficiency diary (PKDD) and the PK deficiency impact assessment (PKDIA).
As previously reported, PYRUKYND®-treated patients in the ACTIVATE study demonstrated significant improvements in signs, symptoms, and impacts based on these PRO instruments compared with patients receiving placebo. This analysis further revealed that improvements were greater in the patients who met the primary endpoint of hemoglobin response (n=16) and sustained over time.