Massachusetts-based Agios Pharmaceuticals (Nasdaq: AGIO) reported topline Phase II data showing that its oral pyruvate kinase activator tebapivat achieved the trial's primary hemoglobin endpoint in sickle cell disease, but said the results lacked sufficient differentiation to justify further development. The decision leaves the company focused on the more advanced mitapivat, which is awaiting an FDA decision in the same indication.
The Phase II trial randomized 59 participants aged 16 and older 2:2:2:1 to once-daily tebapivat at 2.5 mg, 5.0 mg or 7.5 mg, or placebo, over a 12-week double-blind, placebo-controlled period. Absolute response rates differed only modestly from placebo across dose groups. The primary endpoint—a hemoglobin increase of at least 1.0 g/dL averaged over Weeks 10 through 12 versus baseline—was met by 43.8% (7/16) in the 2.5 mg arm, 47.1% (8/17) in the 5.0 mg arm and 29.4% (5/17) in the 7.5 mg arm, compared with 33.3% (3/9) on placebo. Agios said improvements in hemoglobin and hemolysis markers were observed across all dose levels, consistent with the pyruvate kinase activation mechanism, and that safety and tolerability were consistent with prior sickle cell disease trials involving the class.
The study was designed specifically to characterize tebapivat's dose-response relationship and assess whether its profile diverged meaningfully from other PK activators; based on these results, Agios said it will not advance the program further in sickle cell disease. The company did not disclose specific adverse event rates or the full statistical analysis underlying the topline conclusions, and the dataset represents a single completed dose-finding period rather than longer-term follow-up.