PARAGON TRIAL ENTRESTO FULL

The other is sacubitril, a neprilysin inhibitor, so in many ways Paragon is a test of this mechanism of action in treating heart failure, and could give developers some insight into potential single-agent use of sacubitril. The active ingredient in Diovan, the angiotensin II receptor antagonist valsartan, is one of two in Entresto. Another billionДiovan, which is given in the control arm of Paragon, is in fact one drug that has been tested in this patient group, failing to show a benefitВ on exercise time versus placebo. This could be why Novartis has played down the potential for success of Paragon at the interim read, and why investors and analysts have been cautious about its chances even at the final analysis. Heart failure with preserved ejection fraction, defined in this trial as left ventricular ejection fraction of 45% or more, is responsible for about half of all heart failure cases, and i s growing as a share of all heart failure cases.ДЇinding treatments that prevent death or complications has been more difficult in this type of heart failure, in part because researchers do not completely understand its pathophysiology this in turn means that there is heterogeneity in the population. To qualify for an even earlier halt Entresto will need to show superiority on both the primary endpoint and cardiovascular deathВ at a one-sided statistical significance level of 0.001 or less.Д«ecause Novartis does not believe that Entresto will show a benefit on cardiovascular death at the interim look it expects the trial to proceed to final analysis in 2019, where the pill will need to show superiority below a one-sided statistical significance level of 0.025. The interim analysis will take place after about two thirds of the expected 1,847 cardiovascular events have occurred, which is due by the end of 2018. Secondary endpoints are all-cause mortality, change in New York Heart Association functional class, renal outcomes, and change in score on the Kansas City cardiomyopathy questionnaire. The trial has randomised 4,800 patients to treatment with either Entresto or Diovan, comparing the two on a composite endpoint of cardiovascular death or heart failure hospitalisation. Still, Paragon will have to clear a pretty high bar to be stopped this year. While expectations for an interim win in Paragon-HF are low, it should be remembered that EntrestoвЂ™s first pivotal trial, in heart failure patients with reduced ejection fraction, was halted because it showed early superiority to Vasotec in keeping heart disease patients alive and out of hospital ( Novartis gets surprise heart failure win as ACC data roll in, March 31, 2014). Still, Novartis executives and investors expect the study to continue to a final readout in 2019 the company believes that the new indication could add $1bn in annual sales. The Paragon-HF trial in patients with preserved ejection fraction is due for an interim analysis sometime in the next few months, and if Entresto beats Diovan with a high level of statistical significance the trial could be halted for efficacy. Novartis is running a smaller trial for Entresto in HFpEF ( PARALLAX) that has an expected primary completion of Dec 2019.EntrestoвЂ™s painfully sluggish launch has at last started to gain momentum, and expansion into a less severe form of heart failure could add some thrust to NovartisвЂ™s biggest growth driver.

PARAGON TRIAL ENTRESTO FULL

This leaves the door open for various competitors to obtain first approval for HFpEF, with Lilly/BoehringerвЂ™s Jardiance, which received Fast Track designationВ last month, likely the furthest ahead at this point.В Depending on the full results of the PARAGON-HF trial, there is the possibility that physicians will use Entresto off-label for HFpEF until something is officially approved. Now with the PARAGON-HF topline data, it is highly unlikely that regulators would accept an application for a label update. This is obviously a huge blow to Novartis, as they were hoping that Entresto would be as effective for patients with HFpEF as it is for those with HFrEF. Scott Solomon M.D., the trial co-chair, noted that the full trial results may results in clinically meaningful benefits in patients with HFpEF and that the company will discuss next steps with clinical experts and regulators.The data will be presented at the ESC Congress in September.The primary endpoint of reducing cardiovascular death and total heart failure hospitalizations did not reach reach statistical significance.Novartis announced topline results from the phase 3 PARAGON-HF study evaluating Entresto versus valsartan in HFpEF.Get insight from inThought Research experts on Novartis results from the phase 3 PARAGON-HF clinical trial evaluating Entresto versus valsartan in HFpEF.

Paragon trial entresto