Novartis has reported that the Phase III PARAGON-HF clinical trial of sacubitril/valsartan for heart failure patients with preserved ejection fraction (HFpEF) has failed to meet the primary endpoint.
HFpEF occurs when the ventricles do not relax normally during ventricular filling. However, in these patients the heart muscle contracts normally.
The condition may lead to hospitalisation, poor quality of life, and increased mortality. It currently lacks approved treatments.
Sacubitril/valsartan is indicated for the treatment of heart failure with reduced ejection fraction (HFrEF).
The randomised, double-blind, parallel-group, active-controlled, two-arm, event-driven PARAGON-HF study assessed the long-term safety and efficacy of the therapeutic in 4,822 HFpEF patients.
The primary endpoint of the study is the composite of total heart failure hospitalisations and cardiovascular death. Novartis said that the statistical significance on this endpoint has been ‘narrowly missed’ with sacubitril/valsartan, when compared to valsartan alone.
Results showed that the safety and tolerability observed in the trial were consistent with prior sacubitril/valsartan data.
Novartis chief medical officer John Tsai said: “The totality of evidence from the trial suggests that treatment with sacubitril/valsartan may result in clinically important benefits in HFpEF.
“We will be discussing potential next steps with clinical experts and regulators while we prepare to present the full results at the ESC Congress 2019 in September.”
PARAGON-HF forms part of the FortiHFy clinical programme, which includes more than 40 active or planned trials of sacubitril/valsartan in heart failure indications.
In a previous Phase II study called PARAMOUNT-HF, sacubitril/valsartan led to a greater reduction in NT-proBNP, a cardiac strain biomarker, when compared to valsartan at 12 weeks.