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News
A new heart failure drug shows promise — but the results are complicated. Tovinontrine, a PDE9 inhibitor, boosted a key signaling molecule in both HFrEF and HFpEF patients but failed to reduce NT-proBNP — a standard marker of heart failure severity — at the highest dose. Intriguingly, lower doses showed stronger trends toward NT-proBNP reduction, pointing researchers toward a surprising inverse dose-response relationship.
A heart failure drug hits its target but misses its primary goal — for now. Tovinontrine, a phosphodiesterase 9 (PDE9) inhibitor developed by Cardurion Pharmaceuticals, successfully increased plasma cyclic guanosine monophosphate (cGMP) levels in patients with both reduced and preserved ejection fraction heart failure (HFrEF and HFpEF). However, it failed to significantly reduce NT-proBNP — a key biomarker of heart failure severity — at the highest tested dose of 50 mg twice daily.
The findings, presented at the Heart Failure Society of America Annual Scientific Meeting, come from two trials: Cycle-1REF (529 HFrEF patients) and Cycle-2PEF (277 HFpEF patients). A post hoc analysis of Cycle-1REF revealed a surprising twist: lower doses appeared to produce greater reductions in NT-proBNP, hinting at an inverse dose-response relationship. Researchers caution these findings are hypothesis-generating only.
By the Numbers:
Why it matters: Heart failure remains a leading cause of hospitalization and death worldwide, and new treatment pathways are urgently needed. While tovinontrine's results are mixed, the unexpected inverse dose-response signal could reshape how researchers approach PDE9 inhibition — and the upcoming Phase 2b trial will be a critical next step.
