FDA Grants Empagliflozin Broad Heart Failure Indication

The US Food and Drug Administration (FDA) on February 24th approved empagliflozin for patients with heart failure (HF), regardless of ejection fraction, to reduce the risk of cardiovascular (CV) death and hospitalization for HF.

The agency announcement again expands the label for the sodium glucose contransporter-2 inhibitor (Jardiance, Eli Lilly/Boehringer Ingelheim) which was originally developed and approved in 2014 to treat hyperglycemia in patients with type 2 diabetes (T2D). In 2016, FDA added an indication to reduce the risk of CV death in adults with T2D and established CV disease. That approval was followed most recently (August 2021) by an authorization for empagliflozin to reduce the risk of death and hospitalization in patients with HF with reduced ejection fraction (HFrEF), regardless of T2D status.

“In its phase III trials, empagliflozin has shown a statistically significant and clinically meaningful benefit in patients with heart failure across the spectrum of ejection fraction,” said Javed Butler, MD, chairman, Department of Medicine, University of Mississippi, in a statement from Boehringer Ingelheim.

"Today’s approval means these demonstrated benefits can now help to address a significant unmet need for the approximately 3 million adults in the U.S. with preserved ejection fraction, a form of heart failure that has very limited treatment options.”

This landmark approval is based on results from the EMPORER-Preserved phase 3 clinical trial which enrolled 5988 adults with HF and LVEF >40% and without T2D. Participants were randomized to empagliflozin 10 mg or placebo on top of standard of care therapy. Participant’s mean age was 72 years; 45% were women; mean left ventricular ejection fraction (LVEF) was 54%.

During a median follow-up of 26.2 months, EMPORER-Preserved investigators reported, the primary composite primary endpoint of CV death or hospitalization for HF occurred in 13.8% of the empagliflozin group vs in 17.1% of the placebo group (HR = 0.79; 95% CI, 0.69-0.9; P < .0003). The benefit, study authors wrote, was “mostly attributable to fewer patients being hospitalized for heart failure." The results were consistent across all prespecified subgroups including patients with and without diabetes and did not differ by LVEF.

Adverse events associated with empagliflozin were consistent with the side effect profile for adults with T2D, the most common of which were urinary tract infections and female fungal infections.

“While Jardiance may not be effective in all patients with heart failure, this approval is a significant step forward for patients and our understanding of heart failure,” said Norman Stockbridge, MD, PhD, Director of the Division of Cardiology and Nephrology, FDA Center for Drug Evaluation and Research in the FDA announcement.

Empagliflozin was previously granted priority review designation for this broader HF indication.