PARAGON-HF Misses Primary Endpoint: Novartis

The PARAGON-HF trial, evaluating the safety and efficacy of sacubitril/valsartan versus valsartan alone in patients with heart failure with preserved ejection fraction (HFpEF), has missed its primary endpoint, according to a Novartis announcement.

PARAGON-HF, a double-blind, parallel-group study (n=4,822), represents the largest HFpEF clinical trial conducted to date.  Patients had a history of heart failure hospitalizations and were being treated for HFpEF symptoms and comorbidities. Patients were assigned to either a sacubitril/valsartan combination or to valsartan alone. The primary study endpoint was a composite of total first and recurrent heart failure hospitalizations and cardiovascular death.

“Around half of all heart failure patients, some 13 million people worldwide, are estimated to suffer from HFpEF, and there is currently no approved treatment. We embarked upon the landmark Phase III PARAGON-HF trial to determine whether sacubitril/valsartan could have a meaningful impact on the treatment of HFpEF, as it does in the treatment of heart failure with reduced ejection fraction,” said John McMurray, MD, Professor of Medical Cardiology at University of Glasgow and PARAGON-HF Executive Committee Co-Chair, in a Novartis press release.

The trial “narrowly missed statistical significance for its composite primary endpoint of reducing cardiovascular death and total heart failure hospitalizations,” according to the press release. They announcement also reported that safety and tolerability were consistent with previous data.

“The totality of evidence from the trial suggests that treatment with sacubitril/valsartan may result in clinically important benefits in HFpEF,” said John Tsai, MD, Global Drug Development and Chief Medical Officer at Novartis, in the announcement. “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.”

Huge news!

Yet another neutral trial in HFPEF. His time PARAGON-HF trial of Entresto misses endpoint.

What are we doing with HFPEF?@gcfmd @VPrasadMDMPH @MatthewKonerman @rwyeh @GreggWStone @CMichaelGibson https://t.co/Z2r6nWhg5U

— Venk Murthy MD PhD (@venkmurthy) July 29, 2019

☹️Novartis provides update on Phase III PARAGON-HF trial in heart failure patients with preserved ejection fraction (HFpEF) | Novartis https://t.co/5l6XbEesTQ

— Erik Rafflenbeul (@KardiologieHH) July 29, 2019

Very interested! PARAGON-HF was unique in that its primary endpoint included both first and recurrent heart failure hospitalizations. Something that should have improved power – https://t.co/FgY9KdhIJs pic.twitter.com/8zwphqVP7E

— James Deardorff (@wjdeardorff) July 29, 2019