This is the fourth approval for the drug stemming from the EMPOWER clinical trial program.
According to a press release from Boehringer Ingelheim and Eli Lilly,1 the FDA has approved empagliflozin (Jardiance) 10 mg tablets to reduce the risk of sustained decline in estimated glomerular filtration rate (eGFR), end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease (CKD) at risk of progression.
“This approval provides health care professionals in the US with another treatment option for adults with CKD,” said Katherine Tuttle, MD, executive director for research at Providence Inland Northwest Health, regional principal investigator for the Institute of Translational Health Sciences and professor of medicine at the University of Washington, and steering committee member of the phase 3 EMPA-KIDNEY clinical trial (NCT03594110). “The meaningful benefits that empagliflozin demonstrated…are welcome news for adults living with CKD in this country.”
This approval is the fourth FDA nod for empagliflozin associated with the EMPOWER program. More than 700,000 adults worldwide are enrolled in clinical trials.
“Following previous indications for Jardiance in heart failure and type 2 diabetes, this FDA approval now provides [health care providers]…with an important treatment option for adults living with CKD at risk for progression,” said Leonard Glass, MD, FACE, senior vice president of diabetes global medical affairs at Eli Lilly.
“CKD affects more than 1 in 7 adults in the US, 90% of whom are undiagnosed, and it remains a significantly under-recognized public health crisis,” added Mohamed Eid, MD, MPH, MHA, vice president of clinical development and medical affairs, cardio-renal-metabolism and respiratory medicine at Boehringer Ingelheim. “Hospitalizations account for a third to a half of total health care costs for this population, and disease progression often leads to serious cardiovascular complications and kidney failure, which can require dialysis or transplantation.”
EMPA-KIDNEY was multinational, randomized, double-blind, placebo-controlled clinical trial “designed to reflect the broad range of adults with CKD with or without type 2 diabetes. Over 6600 patients were enrolled; those included had an eGFR ≥20 to <45 mL/min/1.73 m2, or an eGFR ≥45 to <90 mL/min/1.73 m2 with a urine albumin to creatinine ratio of ≥200 mg/g. Patients with both type 2 diabetes and prior atherosclerotic cardiovascular disease with an eGFR below 60 mL/min/1.73 m2, with type 1 diabetes, with a functioning or scheduled kidney transplant, with polycystic kidney disease, or who were on dialysis were excluded from the study.
The primary study outcome was the time to a first event of either cardiovascular death or kidney disease progression, defined as end-stage kidney disease, a sustained decline in eGFR to <10 mL/min/1.73 m2, kidney death, or a sustained decline of ≥40% in eGFR from the time of randomization. Key secondary outcomes included cardiovascular death or hospitalization for heart failure, all-cause hospitalization, and all-cause mortality.
Study results demonstrated that empagliflozin was associated with a 28% relative risk reduction vs placebo (absolute risk reduction, 3.6% per patient-year at risk; HR, 0.72; 95% CI, 0.64-0.82), for the composite primary endpoint of kidney disease progression or cardiovascular death. Event rates were 13.1% and 16.9% for the treatment and placebo groups, respectively.
Notably, the EMPA-KIDNEY trial was the first SGLT2 inhibitor CKD trial “to demonstrate a significant reduction in the risk of first and recurrent hospitalization, a prespecified key secondary endpoint” with a 14% relative risk reduction (HR, 0.86; 95% CI, 0.78-0.95). Researchers found that in the empagliflozin group, 1611 hospitalizations occurred among 960 patients—24.8 events per 100 patient-years—compared with 1895 hospitalizations among 1035 patients, or 29.2 events per 100 patient-years, in the placebo group.