Phase III ACTIVATE study of Pyrukynd in pyruvate kinase deficiency published in NEJM.- Agios Pharma

Pyrukynd is a first-in-class, oral PK activator and the first and only approved disease-modifying treatment for this rare, debilitating, lifelong hemolytic anemia.As reported in the publication, the ACTIVATE study met its primary endpoint, with 40 percent of patients randomized to Pyrukynd achieving a hemoglobin response, defined as a minimum 1.5 g/dL increase in hemoglobin concentration from baseline sustained at two or more scheduled assessments at Weeks 16, 20 and 24 during the fixed-dose period, compared to 0 patients randomized to placebo (2-sided p<0.001). patients who received pyrukynd had a significantly greater response than those who received placebo with respect to each secondary endpoint, including average change from baseline in hemoglobin level; average change from baseline in markers of hemolysis including indirect bilirubin, lactate dehydrogenase (ldh) and haptoglobin levels; average change from baseline in markers of hematopoietic activity (reticulocyte percentage); and change from baseline in two pk deficiency–specific patient-reported outcome measures.></0.001).>

The most common adverse events were nausea (in seven patients [18%] in the Pyrukynd group and nine patients [23%] in the placebo group) and headache (in six patients [15%] and 13 patients [33%], respectively). Adverse events of grade 3 or higher occurred in 10 patients (25%) who received Pyrukynd and five patients (13%) who received placebo.

See: "Mitapivat versus Placebo for Pyruvate Kinase Deficiency." Hanny Al-Samkari et al. N Engl J Med 2022; 386:1432-1442 April 14, 2022 DOI: 10.1056/NEJMoa2116634