FDA advisory panel narrowly votes in favor of expanded approval for empagliflozin

An FDA advisory panel narrowly voted on June 28 in favor of an expanded indication for empagliflozin (Jardiance), an oral medication that is FDA-approved to treat adults with type 2 diabetes.

In a 12-11 vote, the FDA’s Endocrine and Metabolic Drug Advisory Committee determined that evidence from a postmarketing trial showed that empagliflozin reduced cardiovascular death in adults with type 2 diabetes and cardiovascular disease.

The FDA is not required to follow the advice of its advisory panels when making approval decisions.

When the FDA approved empagliflozin in August 2014, the agency required the drug’s manufacturers (Eli Lilly and Boehringer Ingelheim) to conduct four additional studies, including a cardiovascular outcomes trial.

The companies published data from that study, known as the EMPA-REG OUTCOME trial, in the New England Journal of Medicine in September 2015. The results were simultaneously presented at the European Association for the Study of Diabetes conference in Sweden.

During the randomized, double-blind study, patients who received empagliflozin had a 14 percent reduction compared with a placebo group in the primary endpoint of a major adverse cardiovascular event, which was defined as cardiovascular death, nonfatal MI or nonfatal stroke.

After a median follow-up of 3.1 years, patients in the empagliflozin group had a 38 percent reduction in cardiovascular death compared with the placebo group. The groups had no significant differences with regards to nonfatal MI or nonfatal stroke. All patients also received the standard of care medications, including glucose-lower agents and cardiovascular drugs.

The FDA committee noted that 124 deaths (71 in the empagliflozin group and 53 in the placebo group) were categorized as “non-assessable” and were presumed as cardiovascular deaths. A sensitivity analysis that removed the “non-assessable” deaths from the primary endpoint showed the empagliflozin was not superior to placebo. However, sensitivity analyses that excluded the “non-assessable” deaths showed that empagliflozin still reduced cardiovascular death and all-cause mortality.

Empagliflozin is the first medication for type 2 diabetes to show a reduction in the risk of cardiovascular death. The drug is in a class of medications known as sodium glucose co-transporter 2 (SGLT2) inhibitors. The two other FDA-approved SGLT2 inhibitors are dapagliflozin (Farxiga) and canagliflozin (Invokana).

The recommended dose of empagliflozin is 10 mg once daily, although patients may also take 25 mg if they need additional glucose lowering.