FDA Advisors Narrowly Back Approval of Empagliflozin (Jardiance) for Cardiovascular Indication

Drug squeaks by on 12-to-11 vote

An FDA advisory committee has voted 12-to-11 that substantial evidence exists to establish that empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) reduces cardiovascular (CV) death in adults with type-2 diabetes (T2D) and established CV disease. Empagliflozin is the only oral T2D medication shown in a clinical trial to reduce the risk of CV death.

The recommendation was made by the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee based on data from the long-term, multicenter, randomized, double-blind, placebo-controlled EMPA-REG OUTCOME trial, which involved more than 7,000 patients with T2D and established CV disease. The study assessed the effect of empagliflozin (10 mg or 25 mg once daily) added to standard of care (SoC) compared with placebo added to SoC. SoC consisted of glucose-lowering agents and CV drugs (including for blood pressure and cholesterol). The study’s primary endpoint was the time to first occurrence of CV death, nonfatal heart attack, or nonfatal stroke.

During a median follow-up period of 3.1 years, empagliflozin significantly reduced the risk of the combined endpoint of CV death, nonfatal heart attack, or nonfatal stroke by 14% when added to SoC in adults with T2D and established CV disease. The primary finding was driven by a 38% reduction in CV death, with no significant difference in the risk of nonfatal heart attack or nonfatal stroke.

Approximately 29 million Americans and an estimated 415 million people worldwide have diabetes, and nearly 28% of Americans with diabetes—totaling eight million people—are undiagnosed. In the United States, approximately 12% of people 20 years of age and older have diabetes. T2D is the most common type, accounting for an estimated 90% to 95% of all diagnosed adult diabetes cases in the U.S.

Because of the complications associated with diabetes, such as high blood sugar, hypertension, and obesity, CV disease is a major complication and the leading cause of death associated with diabetes. People with diabetes are two to four times more likely to develop CV disease than are people without diabetes. In 2015, diabetes caused 5 million deaths worldwide, with CV disease as the leading cause. Approximately 50% of deaths in people with T2D worldwide are caused by CV disease. In the U.S., health care costs for managing CV conditions in patients with diabetes totaled more than $23 billion dollars in 2012.

Empagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2D. It is not for people with type-1 diabetes or diabetic ketoacidosis.

Sources: Eli Lilly; June 28, 2016; and Jardiance Prescribing Information; August 2014.