FDA Approves Empagliflozin for Heart Failure with Reduced Ejection Fraction

The new indication is supported by phase 3 findings showing a 25% reduced risk of hospitalization or death associated with heart failure when taking the once-daily drug.

The US Food and Drug Administration (FDA) has approved empagliflozin 10 mg (Jardiance) for the reduced risk of cardiovascular death plus hospitalization from heart failure (HF) among adults with HF with reduced ejection fraction (HFrEF).

The Eli Lilly and Company agent is now indicated for initiated treatment for adults with HFrEF at estimated Glomerular Filtration Rates (eGFR) as low as 20 mL/min/1.73 m2, providing another treatment option for patients burdened with the condition linked to various cardiovascular, cardiometabolic, and renal risks.

“Heart failure is a chronic, debilitating cardio-renal-metabolic condition affecting over 60 million people worldwide,” Javed Butler, MD, Chairman of the Department of Medicine at University of Mississippi, said in a statement. “As the prevalence of heart failure continues to rise, the need for new treatment options is critical. Empagliflozin is a vital new therapeutic option to reduce the risk of cardiovascular death and hospitalization for adults with (HFrEF)."

The newest FDA approval for empagliflozin is based on findings from the phase 3, international, double-blind EMPEROR-Reduced trial comparing 10 mg therapy versus placebo to standard of care in 3730 adults with and without type 2 diabetes who had HF and a left ventricular ejection fraction (LVEF) of ≤40%. Investigators sought a primary composite endpoint of time to cardiovascular death or hospitalization for HF.

Patients were randomized to either once-daily empagliflozin 10 mg (n = 1863) or placebo (n = 1867), plus guideline-directed HF treatment. At randomization, 75% of patients had New York Heart Association (NYHA) functional class II HF. Median follow-up duration was 16 months.

Empaglofizin was associated with a 25% relative risk reduction in composite endpoint versus placebo, and a 5.3% absolute risk reduction (HR, 0.75; 95% CI, 0.65 – 0.86). In key secondary endpoint assessment, the biologic was additionally associated with a 30% relative risk reduction for first and recurrent hospitalization for HF (HR, 0.70; 95% CI, 0.58 – 0.85).

The observed safety profile of empagliflozin in EMPEROR-Reduced was consistent with that observed in previous clinical trials. Empagliflozin is contraindicated in patients with hypersensitivity to the therapy or any of its excipients, as well as in patients on dialysis. It also not indicated for patients with type 1 diabetes, as it could increase risk of diabetic ketoacidosis.

Approximately half of all patients with HF die within 5 years of diagnosis, with mortality risk increasing with each HF-related hospitalization, noted Mohamed Eid, MD, MPH, MHA, vice president of Clinical Development and Medical Affairs, Cardio-Metabolism & Respiratory Medicine at Boehringer Ingelheim.

“Today's FDA approval of Jardiance in heart failure with reduced ejection fraction, which follows authorization for use in the EU by the European Commission in June, marks an important milestone in our journey to help transform care for adults with heart failure,” Eid said in a statement. “We look forward to continuing to investigate the potential benefit of Jardiance across cardio-renal-metabolic conditions."