FDA Approves Empagliflozin for CKD treatment, regardless of diabetes status

The US Food and Drug Administration has approved another SGLT2 Inhibitor Empagliflozin for treatment of CKD regardless of diabetes status.

Jardiance® (empagliflozin) 10 mg tablets have  been  approved 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, Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced.

Jardiance is not recommended for use to improve glycemic control in patients with type 1 diabetes. It may increase the risk of diabetic ketoacidosis in these patients. Jardiance is not recommended for use to improve glycemic control in patients with type 2 diabetes with an eGFR less than 30 mL/min/1.73 m². Jardiance is likely to be ineffective in this setting based upon its mechanism of action. Jardiance is not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of intravenous immunosuppressive therapy or greater than 45 mg of prednisone or equivalent for kidney disease. Jardiance is not expected to be effective in these populations.

"This approval provides healthcare professionals in the U.S. with another treatment option for adults with CKD that can reduce the risk of kidney function decline, kidney failure, cardiovascular death and hospitalizations," said Katherine Tuttle, M.D., Executive Director for Research, Providence Inland Northwest Health, Regional Principal investigator for the Institute of Translational Health Sciences and Professor of Medicine at the University of Washington, and EMPA-KIDNEY steering committee member. "The meaningful benefits that empagliflozin demonstrated in the EMPA-KIDNEY phase III trial are welcome news for adults living with CKD in this country."

"CKD affects more than one in seven adults in the U.S., 90% of whom are undiagnosed, and it remains a significantly under-recognized public health crisis," said Mohamed Eid, M.D., M.P.H., M.H.A., vice president, Clinical Development & Medical Affairs, Cardio-Renal-Metabolism & Respiratory Medicine, Boehringer Ingelheim Pharmaceuticals, Inc. "Hospitalizations account for a third to a half of total healthcare costs for this population, and disease progression often leads to serious cardiovascular complications and kidney failure, which can require dialysis or transplantation. Given the clinically demonstrated benefits of Jardiance, we are proud to now be able to offer this option to adults with CKD at risk for progression."

Jardiance is contraindicated in people with hypersensitivity to empagliflozin or any of the excipients in Jardiance, as reactions such as angioedema have occurred. Please see additional Important Safety Information below.

EMPA-KIDNEY was a large trial designed to reflect the broad range of adults with CKD with or without type 2 diabetes. Based on the trial inclusion/exclusion criteria, over 6,600 patients were enrolled. Patients 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 ≥200 mg/g. Included patients were deemed appropriate for treatment with an SGLT2 inhibitor by a local investigator. Patients were excluded if they had both type 2 diabetes and prior atherosclerotic cardiovascular disease with eGFR below 60 mL/min/1.73 m², had type 1 diabetes, had a functioning or scheduled kidney transplant, were on dialysis, had polycystic kidney disease, or required or had a recent history of intravenous immunosuppressive therapy or greater than 45 mg of prednisone or equivalent for kidney disease.

In EMPA-KIDNEY, Jardiance demonstrated a 28% relative risk reduction (absolute risk reduction 3.6% per patient-year at risk, HR=0.72; 95% CI 0.64 to 0.82; P<0.0001) compared with placebo, both on top of standard care, for the composite primary endpoint of kidney disease progression* or cardiovascular death. The event rate for Jardiance was 13.1% (432/3304) and for placebo was 16.9% (558/3305). EMPA-KIDNEY is the first SGLT2 inhibitor CKD trial to demonstrate a significant reduction in the risk of first and recurrent hospitalization, a pre-specified key secondary endpoint, with a 14% relative risk reduction (HR=0.86; 95% CI 0.78 to 0.95; p=0.0025) with Jardiance versus placebo. In the Jardiance group, 1,611 hospitalizations occurred among 960 patients (24.8 events per 100 patient-years). In the placebo group, 1,895 hospitalizations occurred among 1,035 patients (29.2 events per 100 patient-years).

This milestone marks the fourth FDA approval for Jardiance stemming from the EMPOWER program. With more than 700,000 adults enrolled worldwide in clinical trials, EMPOWER reinforces the long-term commitment of the Boehringer Ingelheim and Lilly Alliance to improve outcomes for people living with cardio-renal-metabolic conditions.

"Following previous indications for Jardiance in heart failure and type 2 diabetes, this FDA approval now provides physicians, including nephrologists, with an important treatment option for adults living with CKD at risk for progression," said Leonard Glass, M.D., F.A.C.E., senior vice president, Diabetes Global Medical Affairs, Lilly. "Alongside the recent CKD approval for Jardiance in the EU, this decision further bolsters our efforts to support this community globally."

*Kidney disease progression: Defined as end-stage kidney disease (the initiation of maintenance dialysis or receipt of a kidney transplant), a sustained decline in estimated glomerular filtration rate (eGFR) to below 10 mL/min/1.73 m², kidney death or a sustained decline of at least 40% in eGFR from randomization).

About EMPA-KIDNEY

EMPA-KIDNEY (NCT03594110) is a multinational, randomized, double-blind, placebo-controlled clinical trial, designed to evaluate the effect of Jardiance on kidney disease progression and cardiovascular mortality risk. The primary outcome is defined as time to a first event of either cardiovascular death or kidney disease progression, defined as end-stage kidney disease (the need for kidney replacement therapy such as dialysis or kidney transplantation), a sustained decline in eGFR to <10 mL/min/1.73 m², kidney death or a sustained decline of ≥40% in eGFR from randomization. Key secondary outcomes include cardiovascular death or hospitalization for heart failure, all-cause hospitalization and all-cause mortality. EMPA-KIDNEY includes 6,609 adults from eight countries with CKD, both with and without diabetes, who were randomized to receive either Jardiance 10 mg or placebo, once daily, both on top of current standard of care.

Patients 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 ≥200 mg/g. Included patients were deemed appropriate for treatment with an SGLT2 inhibitor by a local investigator. Patients were excluded if they had both type 2 diabetes and prior atherosclerotic cardiovascular disease with eGFR below 60 mL/min/1.73 m2, had type 1 diabetes, had a functioning or scheduled kidney transplant, were on dialysis, had polycystic kidney disease, or required or had a recent history of intravenous immunosuppressive therapy or greater than 45 mg of prednisone or equivalent for kidney disease.

What is JARDIANCE?

JARDIANCE is a prescription medicine used to:

• reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure, when the heart cannot pump enough blood to the rest of your body

• reduce the risk of further worsening of kidney disease, end-stage kidney disease (ESKD), death due to cardiovascular disease, and hospitalization in adults with chronic kidney disease

• reduce the risk of cardiovascular death in adults with type 2 diabetes who also have known cardiovascular disease

• lower blood sugar along with diet and exercise in adults and children who are 10 years of age and older with type 2 diabetes

JARDIANCE is not for use to lower blood sugar in people with type 1 diabetes. It may increase their risk of diabetic ketoacidosis (increased ketones in the blood or urine).

JARDIANCE is not for use to lower blood sugar in people with type 2 diabetes who have severe kidney problems, because it may not work.

JARDIANCE is not for people with polycystic kidney disease, or who are taking or have recently received certain types of immunosuppressive therapy to treat kidney disease. JARDIANCE is not expected to work if you have these conditions.