FDA Approves Empagliflozin to Treat HFrEF Regardless of T2D Status

The FDA has approved Boehringer Ingelheim and Eli Lilly’s empagliflozin (Jardiance) for heart failure with reduced ejection fraction (HFrEF), adding an additional indication to the drug for use in patients with type 2 diabetes (T2D).

The announcement comes after the agency accepted a supplemental New Drug Application (sNDA) for the sodium glucose co-transporter 2 (SGLT2) inhibitor in January 2021. The drug was first approved in 2014.

According to a statement from Boehringer Ingelheim, approximately half of patients with heart failure (HF) die within 5 years of diagnosis, while HF accounts for over 1 million hospitalizations annually in the United States. HFrEF also makes up more than half of HF cases.

The “approval is significant for the millions of people diagnosed with this form of heart failure, offering additional hope for those who have seen limited new treatment options over the last decade,” said Jeff Emmick, MD, PhD, the vice president of product development at Eli Lilly.

Specifically, empagliflozin 10 mg is now indicated to reduce the risk of cardiovascular death plus hospitalization for HF in HFrEF patients—regardless of T2D status— and can be initiated in adults with an estimated glomerular filtration rate (eGFR)as low as 20 mL/min/1.73 m².

The approval is based on results of the EMPEROR-reduced phase III trial, findings of which were presented at the 2020 European Society of Cardiology conference.

Among a group of patients with serious HFrEF—the majority had left ventricular ejection fraction of 40% or less—empagliflozin produced the following results:

• Met its primary end point, a combination of reducing the risk of cardiovascular death or hospitalization for heart failure by 25%, with most of that result driven by a 31% lower risk of hospitalization for heart failure (HR, 0.75; 95% CI, 0.65-0.86, P < .001).
• Reduced the risk of first or future hospitalizations for heart failure by 30% (HR, 0.70; 95% CI, 0.58-0.85, P < .001).
• Reduced renal events by 50%, (HR, 0.50; 95% CI, 0.32-0.77, P = .0019)
• Produced slower rate of annual decline in the eGFR than placebo (–0.55 vs –2.28 ml per minute per 1.73 m² of body surface area per year, P < .001).

Additional studies are being conducted to evaluate the drug’s performance in patients heart failure with preserved ejection fraction (HFpEF), for which 1 treatment is approved, or chronic kidney disease.

“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. We look forward to continuing to investigate the potential benefit of Jardiance across cardio-renal-metabolic conditions,” said Mohamed Eid, MD, MPH, MHA, vice president of clinical development and medical affairs, cardio-metabolism and respiratory medicine at Boehringer Ingelheim.

Along with diet and exercise, empagliflozin has been shown to lower blood sugar in individuals with T2D and reduced the risk of cardiovascular death in these patients with cardiovascular disease.