For all those who still don't get it, here is what happens to a CHF drug when you hit your primary endpoint of hospitalizations and have little impact on the secondary (most clinically significant and gold standard) endpoint of mortality - FAILURE!

SI is correct is stating their results should cause a paradigm shift in this apparently fairly useless surrogate endpoint of hospitalizations. We don't need to just rely on the DREAM-HF results to demonstrate the weakness of this endpoint, the big pharma studies are also building the case for it. Yet, I wonder how many have been able to hoodwink the FDA into getting approval with studies using it as a primary endpoint with drugs which will never have any significant impact on saving lives?

I am by no means a statistical expert, but I know how to correlate two endpoints to each other. And those really clever stats people within Pharma appears have done a nice job on regulators to convince them some very complex event driven, hospitilsation rate statistics used to shorten studies and make them more 'efficient' are somehow correlated to mortality. Well, the correlation appears very weak in the real world. And here is more proof, from Big Pharma themselves:

Amgen, Cytokinetics’ heart failure drug disappoints in phase 3

Drug hit primary endpoint but missed secondary endpoint of reduction in cardiovascular death

A heart failure drug initially developed by Cytokinetics and taken into phase 3 development by Amgen and Servier has widely disappointed investors despite showing some statistically significant results.

The results from theGALACTIC-HF study show that treatment with the drug, omecamtiv mecarbil, hit the primary endpoint of statistical significance on a measure of reduction in hospitalisation or other urgent care for heart failure. Compared to placebo, the treatment reduced the risk by 8%, a modest benefit in the high-risk patient population.

However, Amgen’s drug missed the mark on the secondary endpoint of reduction in cardiovascular death and was unable to help high-risk patients to live longer compared to placebo.

Following the publication of the results, shares in Amgen dropped down by 4.6%, with shares in California-based Cytokinetics falling by 43%.

Omecamtiv mecarbil, originally developed by Cytokinetics, is designed to increase the duration of cardiac muscle contractility and improve cardiac muscle performance. It works by targeting myosin, a protein that converts chemical energy into mechanical force within the heart.

"The outcomes observed in GALACTIC-HF further the understanding of treating heart failure, a devastating disease in which half of heart failure patients will die within five years of initial hospitalisation," said David M. Reese, executive vice president of research and development at Amgen.

"At Amgen, we remain committed to developing and delivering transformative medicines that improve the lives of patients with cardiovascular disease,” he added.

Amgen is set to present additional analyses of the data and results from the GALACTIC-HF trial at the upcoming American Heart Association (AHA) Scientific Sessions 2020.

Heart failure has become an increasingly competitive therapy area over the last few years, as a new generation of therapies enter the market.

This includes Novartis’ Entresto (sacubitril/valsartan) and AstraZeneca’s Farxiga (dapagliflozin) which have been steadily adding indications to their labels since initial approval.

Also coming through the pipeline is Merck & Co and Bayer’s high-risk heart failure drug vericiguat which is currently being studied in patients with worsening chronic heart failure with reduced ejection fraction (HFrEF).

Earlier this week, Bristol Myers Squibb (BMS)announcedthat it was set to acquire cardiovascular specialist MyoKardia for $13.1bn. In the process, BMS will gain the rights to MyoKardia’s investigational treatment mavacamten, which is currently being developed as a treatment for obstructive hypertrophic cardiomyopathy (HCM), wherein the wall between the bottom two chambers of the heart thickens and reduce blood flow.

http://www.pmlive.com/pharma_news/amgen,_cytokinetics_heart_failure_drug_disappoints_in_phase_3_1352875