Lilly announces initiation of EMPEROR HF clinical trial program to assess Jardiance (empagliflozin) in heart failure – March 17, 2017

This morning, Lilly announced the initiation of the EMPEROR (EMPagliflozin outcomE tRial in patients with chrOnic heaRt failure) HF clinical trial program to assess the impact of BI-partnered SGLT-2 inhibitor Jardiance (empagliflozin) on adults with chronic heart failure. The EMPEROR HF program will involve two phase 3 outcomes studies, EMPEROR HF-Preserved and EMPEROR HF-Reduced, which will respectively assess empagliflozin in patients with chronic heart failure with preserved ejection fraction (when the heart muscle contracts normally but the ventricle muscles are stiff; estimated enrollment = 4,100) and reduced ejection fraction (when the heart muscles does not contract effectively; estimated enrollment = 2,800). Both studies have a composite primary endpoint of time to either first event of adjudicated cardiovascular death or adjudicated hospitalization for heart failure and both are expected to complete in 2020. Secondary endpoints include eGFR, time to first occurrence of sustained reduction of eGFR, time to all-cause mortality, time to onset of diabetes, change from baseline in clinical summary score of chronic heart failure, and occurrence of all-cause hospitalization. Though Jardiance is currently indicated as a diabetes drug, the trials will enroll heart failure patients both with and without diabetes, marking the first time that empagliflozin will be evaluated in people without type 2 diabetes. If positive, we expect Lilly/BI will pursue a standalone heart failure indication for empagliflozin, separate from type 2 diabetes, which will greatly increase the indicated population for the drug. Given its expertise in the cardiovascular field, BI is taking the lead with this development program.

 Jardiance is already indicated for the reduction of the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease (the first label of its kind for a diabetes drug!) on the basis of the EMPA-REG OUTCOME trial, which demonstrated an impressive 38% risk reduction for cardiovascular death with empagliflozin compared to placebo (HR=0.62, 95% CI = 0.49-0.77; p<0.001) and showed a 35% reduction in the secondary endpoints of hospitalization for heart failure (HR = 0.65; 95% CI = 0.50-0.85; p=0.002). However, as a secondary endpoint, heart failure findings did not support a specific indication related to heart failure on the label – the EMPEROR HF program offers an opportunity for Lilly/BI to assess the heart failure impact of empagliflozin in a more rigorous manner. We are intrigued to follow the progress of the EMPEROR program, and even more curious to learn whether empagliflozin’s ability to reduce the risk of heart failure will differ between individuals with versus without type 2 diabetes. 

-- by Abigail Dove, Helen Gao, and Kelly Close