FDA Approves Empagliflozin for Adults With Heart Failure

Empagliflozin demonstrated a statistically significant risk reduction in cardiovascular death and hospitalization for heart failure, regardless of ejection fraction.

The FDA has approved empagliflozin (Jardiance, Boehringer Ingelheim) to lower the risk of cardiovascular death and hospitalization for heart failure in adult patients.

Following the FDA action, empagliflozin becomes the first approved heart failure therapy to demonstrate a statistically significant risk reduction in cardiovascular death and hospitalization for heart failure, regardless of ejection fraction, according to Boehringer Ingelheim.

In 2014, the FDA approved empagliflozin as a supplement to diet and exercise to improve glucose control in adults with type 2 diabetes (T2D). The treatment has also been approved to lower the risk of cardiovascular death in adults with T2D and established cardiovascular disease and to reduce the risk of death and hospitalization in patients with heart failure and low ejection fraction. The FDA previously granted priority review for the current indication.

The treatment can be initiated in adults with heart failure with an eGFR as low as 20 mL/min/1.73 m2.

Norman Stockbridge, MD, PhD, director of the Division of Cardiology and Nephrology, FDA Center for Drug Evaluation and Research, said the approval will offer a treatment option for a wider range of patients with heart failure.

“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,” Stockbridge said in a press release. “Coinciding with February’s annual observance of American Heart Month—a reminder for individuals to focus on cardiovascular health—this action will provide physicians another tool to address heart disease.”

The safety and efficacy of empagliflozin as an adjunct to standard of care therapy was evaluated in the phase 3 EMPEROR-Preserved trial. Participants administered empagliflozin 10 mg once-daily (n = 2997) were compared with participants administered a placebo (n = 2991). The main efficacy measurements included the time-to-death from cardiovascular causes or need for hospitalization for heart failure.

Among individuals who received empagliflozin for an average of 2 years, the study found that 14% died from cardiovascular causes or were hospitalized for heart failure, compared to 17% who received the placebo. The investigators said this benefit was largely attributable to fewer patients being hospitalized for heart failure.

"In its phase 3 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 press release. "Today's approval means these demonstrated benefits can now help to address a significant unmet need for the approximately 3 million adults in the US with preserved ejection fraction, a form of heart failure that has very limited treatment options."

Adverse effects (AEs) in clinical studies with empagliflozin for patients with heart failure were consistent with AEs for patients with diabetes. The most common AEs in patients with diabetes were urinary tract infections and female fungal infections. Symptoms of heart failure can include shortness of breath, fatigue, and swelling in the legs.

More than 650,000 people in the United States are affected by heart failure with high mortality rates, highlighting the need for more treatment options for a broader range of patients. Heart failure is more common with age and is the leading cause of hospitalization in patients over 65 years.

"The EMPEROR-Preserved trial demonstrated breakthrough benefits for a widely underserved group of people who have heart failure. With today's news, Jardiance becomes the first and only heart failure treatment to show a statistically significant risk reduction in cardiovascular death and hospitalization for heart failure in adults with heart failure, regardless of ejection fraction," said Mohamed Eid, MD, MPH, MHA, vice president, Clinical Development and Medical Affairs, Cardio-Metabolism & Respiratory Medicine, Boehringer Ingelheim Pharmaceuticals, Inc, in a press release. "This approval, with a decision for use in the EU by the European Commission expected to follow, represents an important milestone in our efforts to redefine heart failure care and advance treatment options for people with a range of cardio-renal-metabolic conditions."

Reference

US FDA approves Jardiance® (empagliflozin) to treat adults with heart failure regardless of left ventricular ejection fraction. Boehringer Ingelheim and Eli Lilly and Company. News release. https://investor.lilly.com/news-releases/news-release-details/us-fda-approves-jardiancer-empagliflozin-treat-adults-heart. February 24, 2022.