FDA Grants Empagliflozin Breakthrough Therapy Designation in HFpEF

The sodium glucose co-transporter 2 (SGLT2) inhibitor reduced cardiovascular death and hospitalization for heart failure by 21% in results presented August 27 during the recent European Society of Cardiology Congress.

On the heels of landmark results presented in the EMPEROR Preserved trial, FDA has granted Breakthrough Therapy designation to empagliflozin for the treatment of heart failure with preserved ejection fraction (HFpEF), the first drug in its class to gain this status.

Boehringer Ingelheim and Eli Lilly and Company, which sell empagliflozin as Jardiance, announced the FDA decision in a statement early today.

The sodium glucose co-transporter 2 (SGLT2) inhibitor reduced cardiovascular death and hospitalization for HF by 21% in results presented August 27 during the recent European Society of Cardiology Congress, with those results driven by a 27% reduction in first and recurrent HF hospitalization. Results were also published in the New England Journal of Medicine.

Principal investigator Stefan Anker, MD, of Charité Campus Virchow Clinic, Berlin, Germany, told The American Journal of Managed Care® that the results showed empagliflozin reduced events regardless of diabetes status and similarly among men and women with HFpEF.

“Looking at these subgroups and other subgroups, we can say that none of the prespecified subgroups tells us anything that there is a subgroup of patients where we shouldn’t use this,” Anker said. “In HFpEF patients, empagliflozin represents a medicine that reduces heart outcomes.”

Empagliflozin offered benefits to patients with ejection fraction up to 65%, which study coauthor Javed Butler, MD, of the University of Mississippi, said represents all but about 10% of patients with HF.

This was by far the best result for dedicated trial for HFpEF. Other trials have shown signals in this condition but have not met their end point. Given the unmet need, earlier this year FDA granted Novartis’ Entresto (sacubitril/valsartan) an expanded indication to treat a broader group of patients based on results across several studies, but this indication does not include patients with up to 65% ejection fraction.

HFpEF accounts for half of the approximately 6 million HF cases in the United States. Incidence of HFpEF is increasing as the population ages, and it is especially common among older women.

“This Breakthrough Therapy designation underscores the potential of Jardiance to help fill a critical need for a clinically proven treatment for people with this highly prevalent, difficult-to-treat condition,” Mohamed Eid, MD, MPH, MHA, vice president, Clinical Development & Medical Affairs, Cardio-Metabolism & Respiratory Medicine, Boehringer Ingelheim Pharmaceuticals, Inc, said in a statement.

“Following the recent FDA approval of Jardiance for heart failure with reduced ejection fraction, this is another important milestone supporting the potential of Jardiance as the first therapy clinically proven to improve outcomes across the full heart failure spectrum.”

FDA’s Breakthrough Therapy designation offers an opportunity for expedited review of therapies that can treat a serious condition when preliminary clinical evidence shows a substantial improvement over available therapies on a clinically significant end point.

"Given the scarcity of treatment options for this debilitating condition, the benefits demonstrated in the EMPEROR-Preserved trial constituted a major clinical breakthrough," said Jeff Emmick, MD, PhD, vice president, Product Development, Lilly.

Empagliflozin and other drugs in the SGLT2 inhibitor class were first developed to treat patients with type 2 diabetes by lowering glucose through a unique mechanism that targets a protein allowing glucose to be excreted from the body through the urine. Separately, FDA granted Fast Track designation for empagliflozin to reduce the risk of cardiovascular death and hospitalization for HF.

Last month, results from an earlier trial, EMPEROR-Reduced, led to an FDA approval for HF with reduced ejection fraction.