Empagliflozin Meets Primary End Point for Heart Failure With Reduced Ejection Fraction

Empagliflozin, the sodium glucose co-transporter-2 (SGLT2) inhibitor sold as Jardiance, has met its primary end point in a trial testing whether the drug can trim the risk of heart failure with reduced ejection fraction in patients with and without diabetes. Announcement of topline results for the study, called EMPEROR-Reduced, came early today from the drug’s sponsors, Boehringer Ingelheim and Lilly.

The primary end point, as spelled out in the European Journal of Heart Failure, is a composite of cardiovascular death and hospitalization for heart failure. The statement from the drug’s sponsors did not discuss secondary end points, but the study protocol in the journal said the trial “will also evaluate the effects of empagliflozin on renal function, cardiovascular death, all-cause mortality, and recurrent hospitalization events.”

“With these positive top-line results from the EMPEROR-Reduced trial, we are excited to mark another important advancement for Jardiance,” Mohamed Eid, MD, MPH, MHA, vice president, Clinical Development & Medical Affairs, Cardio-Metabolism & Respiratory Medicine, Boehringer Ingelheim Pharmaceuticals, Inc., said in a statement. “There is an urgent need for new heart failure treatments, and these results show promise for the potential role Jardiance can play in improving the lives of adults living with this condition.”

“These results build upon the already established cardiovascular benefits of Jardiance in adults living with type 2 diabetes and cardiovascular disease,” said Jeff Emmick, MD, PhD, vice president, Product Development, Lilly. “Metabolic conditions that affect the heart and kidneys can lead to serious consequences, including hospitalizations and death. Through our EMPOWER clinical program, we are committed to advancing knowledge about these devastating clinical outcomes. We look forward to seeing how Jardiance can help adults around the world living with these conditions.”

Results for EMPEROR-Reduced (for the 10 mg dose) have been highly anticipated, as they are expected to set of a new round of competition in the drug class, which was first developed to treat type 2 diabetes (T2D). A competitor, dapagliflozin (Farxiga, AstraZeneca), has already shown its ability to treat this type of heart failure and received this FDA indication in May.

But when investigators present results for EMPEROR-Reduced next month during the virtual meeting of the European Society of Cardiology (ESC) Congress 2020, they will be returning to where it all began 5 years, ago, when results from the cardiovascular outcomes trial EMPA-REG OUTCOME stunned the scientific community with data that showed a T2D, designed to lower blood glucose, also prevented heart attacks and cardiovascular death. A secondary endpoint suggested remarkable powers to reduce hospitalization from heart failure, and the race was on to test competitors in the drug class specifically for this purpose.

In an email, Eid said that a full discussion of secondary end points, including quality of life, will come at the ESC presentation on August 29, and that regulatory filings will take place during the 2020 calendar year.

Besides EMPEROR-Reduced, a second trial, EMPEROR-Preserved, continues to study whether the SGLT2 inhibitor can reduce the risk of heart failure in patients with preserved ejection fraction, a condition for which there are no approved therapies. This trial has enrolled more patients (5990 in EMPEROR-Preserved vs 3730 in EMPEROR-Reduced), and results are not expected until 2021.

Heart failure occurs when the body cannot effectively pump blood throughout the body. It affects around 6.5 million adults in the United States and was a contributing cause of 1 in 8 deaths in 2017, according to the CDC. It is a common reason for hospitalization and a costly one, too; since the passage of the Affordable Care Act, health systems are scrutinized if they have repeated hospital readmissions of Medicare patients for heart failure. This has created incentives to find more effective and efficient ways to prevent and treat the condition.