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Health · Drug development · published 2026-10-11 · via MedPage Today

PDE9 Inhibitor Misses Endpoints in Heart Failure Trials, Lower Dose to Be Tested

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Image via MedPage Today

Two phase II placebo-controlled trials of the PDE9 inhibitor tovinontrine did not show expected reductions in NT-proBNP in heart failure with reduced or preserved ejection fraction. Researchers suspect the 50 mg twice-daily dose was too high, because lower doses produced more favorable NT-proBNP changes in one trial. A new phase IIb trial, CYCLE-3, will test a lower dose in HFrEF beginning in 2027.

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Tovinontrine is a PDE9 inhibitor being studied in heart failure. In CYCLE-1, people with HFrEF received doses from 2.5 to 50 mg twice daily or placebo. The 50 mg dose did not significantly lower NT-proBNP versus placebo, while 25 mg showed a borderline signal. Median NT-proBNP changes were best at the lowest dose, suggesting an inverse dose relationship.

CYCLE-2 tested 50 mg twice daily in HFpEF and found

Expanded detail and Context are AI-generated analysis; the linked article remains the authoritative source.
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This summary is Al-enhanced to contain extended analysis and broader social context. The original is {NAME); the linked article is the authoritative source. Original headline: “And It's Back to the Drawing Board for PDE9 Inhibition in Heart Failure.” Browse more stories.