FDA Panel Narrowly OKs Empagliflozin CV Benefit Claim

If the full FDA accepts the panel's narrow recommendation, the type 2 diabetes therapy could enjoy a preferred status above its rivals in the SGLT2 market.

An FDA advisory panel has voted 12-11 that substantial evidence exists for Boehringer Ingelheim and Eli Lilly to claim that empagliflozin, marketed as Jardiance, reduces the risk of cardiovascular (CV) death. If the full FDA accepts this recommendation, the SGLT2 inhibitor would have a significant edge over its competitors, canagliflozin and dapagliflozin.

The narrow vote of FDA’s Endocrinologic and Metabolic Drugs Advisory Committee surprised some analysts, given the results of the EMPA-REG OUTCOME trial that received widespread attention when findings were presented in September 2015. The trial involved 7000 patients in 42 countries and found that after a median period of 3.1 years, empagliflozin reduced the risk of CV death, of non-fatal heart attack and of non-fatal stroke by 14%. Risk of CV death was reduced 38% with no significant difference in non-fatal heart attack or stroke.

At that time, empagliflozin was the first therapy for type 2 diabetes (T2D) to produce such a result; since then, liraglutide, a GLP-1 receptor agonist, has produced CV benefits, based on results from the LEADER trial presented last month at the American Diabetes Association Scientific Sessions in New Orleans. LEADER showed that liraglutide reduced CV death risk by 22%.

These results make it a “very exciting time” for physicians treating patients with T2D, according to experts convened this spring by The American Journal of Managed Care to discuss the outcomes of recent clinical trials.

“Despite the significant advances in the prevention and treatment of cardiovascular disease over the past several decades, more than half of adults with type 2 diabetes worldwide still die due to cardiovascular causes,” said Jeff Emmick, MD, PhD, vice president of product development at Lilly Diabetes, in a statement. “The cardioprotective benefit of Jardiance could provide an additional option to physicians to reduce the risk of cardiovascular death in their patients with type 2 diabetes.”

FDA has required CV outcomes trials since a meta-analysis in the New England Journal of Medicine led to questions about the safety of rosiglitazone and subsequent limits on that once-popular therapy. The main reason for the trials is to show that new diabetes and obesity drugs are not unsafe, and indeed the panel voted unanimously that empagliflozin posed no risk. Expanding the label to say that the therapy produces an actual benefit, Evercore ISI analyst Mark Schoenebaum wrote to clients, typically requires more than a single study.

Competitors canagliflozin and dapagliflozin must wait until 2017 and 2019, respectively, for similar results to confirm whether the results seen in EMPA-REG are a class effect or apply to empagliflozin only. In November 2015, Yale Diabetes Center’s Silvio Inzucchi, MD, warned reporters gathered at the American Heart Association Scientific Session not to assume anything, as scientists have been burned in the past by making such leaps.