Jardiance 1 Step Closer to FDA Approval for Use in Heart Failure

The FDA today accepted Boehringer Ingelheim and Eli Lilly’s supplemental New Drug Application (sNDA) for Jardiance (empagliflozin), the oral sodium glucose co-transporter 2 (SGLT2) inhibitor being investigated for use in patients with heart failure.

Having already been approved by the FDA in 2014 for use in patients with type 2 diabetes (T2D), as an adjunct to diet and exercise for better glycemic control, an indication for heart failure—reduced ejection fraction (HFrEF), specifically—would expand the treatment pool for a condition with a nearly 50% 5-year mortality rate.

Jardiance received a Fast Track designation in March of last year for use in chronic kidney disease, as part of the EMPEROR program, consisting of the EMPEROR-Reduced and Preserved trials. There are currently no approved treatments for heart failure with preserved ejection fraction, although Entresto (sacubitril/valsartan) aims to be the first.

“New treatments for heart failure are needed to help reduce the risk of death in those affected by this chronic, debilitating illness,” said Mohamed Eid, MD, MPH, MHA, vice president, Clinical Development & Medical Affairs, Cardio-Metabolism & Respiratory Medicine, Boehringer Ingelheim Pharmaceuticals, Inc, in a statement. “We look forward to working with the FDA to potentially expand the number of adults who may benefit from Jardiance to include those affected by heart failure with reduced ejection fraction.”

It was back in July 2020 that data were released from the EMPEROR-Reduced trial showing that empagliflozin met the primary end point of reduced cardiovascular death (CVD) and heart failure hospitalization, regardless of diabetes status. At that time, too, Eid noted the urgency for new heart failure treatments. “With these positive top-line results from the EMPEROR-Reduced trial, we are excited to mark another important advancement for Jardiance,” he said.

These EMPEROR-Reduced data serve as the basis for the sNDA acceptance. In particular, there was a 25% decline seen in the primary composite end point of CVD and hospitalization following administration of the once-daily tablet. For hospitalization, too, empagliflozin has been linked to a 20% reduction in care costs among patients with comorbid T2D and CVD.

In addition to the primary end point, empagliflozin may also reduce the rate at which kidney function worsens in patients with HFrEF. Also known as systolic heart failure, this condition occurs when weakened left ventricle muscles can’t fully contract, resulting in a lack of oxygen-rich blood going out to the body.

The acceptance of the sNDA continues the upward mobility of results seen in 2015 in the EMPA-REG OUTCOME trial for empagliflozin, where the drug was first shown to reduce CVD in patients with T2D. SGLT2 inhibitors were originally developed to treat T2D; heart failure was not a primary end point, noted Javed Butler, MD, MPH, MBA, chairman of the Department of Medicine at the University of Mississippi. “It was a secondary endpoint. Nobody was expecting that degree of robust benefit for heart failure that we saw,” he said.

Adverse effects of empagliflozin include dehydration, vaginal and penis yeast infections, ketoacidosis, hypoglycemia, urinary tract infections, and necrotizing fasciitis. Contraindications include those for women who currently or are planning to breastfeed, women who are pregnant or trying to become pregnant, and patients with liver or kidney problems.