Data points to big win for Jardiance in hard-to-treat heart failure

The data is now in from the EMPEROR-Preserved study of Boehringer Ingelheim and Eli Lilly's Jardiance in heart failure with preserved ejection fraction (HFpEF), and suggest the drug performs better than Novartis' Entresto – currently the only approved option for these patients.

SGLT2 inhibitor Jardiance (empagliflozin) reduced a composite of cardiovascular (CV) death or hospitalisations for heart failure by a significant 21% compared to placebo in HFpEF, regardless of diabetes status, according to results presented at the European Society of Cardiology (ESC) meeting over the weekend.

The improvement compares to a 13% reduction in the same endpoint with Entresto (sacubitril/valsartan) in the PARAGON-HF trial, which secured the first-ever FDA approval in HFpEF earlier this year.

That result did not meet statistical significance, but the FDA decided it was a solid enough result to allow cardiologists to use their discretion in prescribing Entresto for patients with HFpEF.

Jardiance's improvement was driven by hospitalisations, with a 9% reduction in death that didn't reach statistical significance, although that shouldn't stand in the way of approval for HFpEF given the minimal treatment options available to patients.

Boehringer and Lilly teased the result last month, but had not revealed the actual data ahead of the ESC presentation and simultaneous publication in the New England Journal of Medicine. The companies say they now intend to file for approval of Jardiance in HFpEF before the end of the year.

"These results represent the first trial to show unequivocal benefit of any drug on major heart failure outcomes in patients with HFpEF," said Stefan Anker of Charité Berlin, Germany, at an ESC press conference on the new data.

The result was described as "practice changing" by Carlos Aguiar of Hospital Santa Cruz in Portugal at the briefing, while an editorial accompanying the NEJM article by Mark Drazner of University of Texas Southwestern Medical Centre said it is "a major win against a medical condition that had previously proved formidable."

Jardiance is already approved to treat heart failure with reduced ejection fraction (HFrEF) following positive results in the EMPEROR-Reduced study, which showed a 25% reduction in hospitalisations and cardiovascular death compared to placebo.

The new result allows Boehringer and Lilly to steal a march on AstraZeneca, whose Farxiga/Forxiga (dapagliflozin) has been beating a trail for SGLT2 inhibitors in heart failure, claiming a first-in-class okay for HFrEF last year that has invigorated its sales growth.

AZ is testing Farxiga for HFpEF as well, and its trial – called DELIVER – could generate results before the end of the year or early in 2022.