Tovinontrine 50 mg improves cGMP but shows minimal NT-proBNP effect in HFpEF trial

Results from the phase 2 Cycle-2-PEF trial, presented at the Heart Failure Society of America Annual Scientific Meeting 2026, indicate that a 50 mg dose of tovinontrine improves plasma cGMP levels in patients with chronic heart failure with preserved ejection fraction (HFpEF) but has minimal effect on NT-proBNP levels.

The randomized, double-blind, placebo-controlled study involved 277 patients, with 267 completing the trial. The 50 mg dose was selected to achieve maximal PDE9 inhibition. While preclinical models suggested PDE9 inhibitors could regress hypertrophy, this specific dose failed to lower NT-proBNP, the study's primary endpoint, despite successfully increasing plasma cGMP.