Novartis says late-stage study of Entresto in heart failure patients with preserved ejection fraction "narrowly" misses main goal

Novartis announced Monday that a Phase III study of Entresto (sacubitril/valsartan) versus valsartan in heart failure patients with preserved ejection fraction (HFpEF) failed to meet its primary endpoint. The company noted that the PARAGON-HF trial "narrowly missed statistical significance" for its composite main goal of reducing cardiovascular death and total heart failure hospitalisations.

Entresto is currently approved in the EU for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction, while the drug is authorised in the US for the treatment of heart failure in patients with systolic dysfunction. John Tsai, Novartis' chief medical officer, suggested that "the totality of evidence from the trial suggests that treatment with [Entresto] may result in clinically important benefits in HFpEF," adding "we will be discussing potential next steps with clinical experts and regulators."

In the PARAGON-HF study, 4822 patients with HFpEF, approximately half of whom had a history of heart failure hospitalisations, were randomised to receive Entresto twice daily or valsartan. The trial's primary endpoint is the composite of total heart failure hospitalisations and cardiovascular death. Novartis noted that detailed findings are scheduled to be presented later this year at the annual meeting of the European Society of Cardiology (ESC).

Commenting on the results, Zuercher Kantonalbank analyst Michael Nawrath said the likelihood of a positive outcome in the PARAGON-HF study had been low. "The milder the disease, the higher the hurdle," he noted, adding "it would have been very good for the momentum of Novartis…on a positive outcome."

For related analysis, see ViewPoints: Can Entresto’s ‘clinical importance’ trump statistical significance in HFpEF? 

Earlier this month, Novartis reported that second-quarter sales of Entresto jumped 76% year-over-year to $421 million, with growth fuelled by increased demand in both hospital and ambulatory settings. For related analysis, see ViewPoints: Key takeaways from Novartis' second-quarter earnings, and Drug portfolio snapshot (Q219): Novartis - current and future growth drivers.


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