FDA reviews Empagliflozin's potential for arresting progression of chronic kidney disease

USA: Jardiance (empagliflozin) tablets have received the supplemental New Drug Application (sNDA) from the U.S. Food and Drug Administration (FDA).

Jardiance is being investigated as a potential treatment to reduce the risk of kidney disease progression and cardiovascular death in adults with CKD (chronic kidney disease). 

"There is a significant need for additional therapies that reduce the risk of kidney disease progression and hospitalizations in adults with CKD," 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. "This application acceptance is an important step forward for the approximately 37 million people in the U.S. living with CKD."

The sNDA is based on results from the landmark EMPA-KIDNEY phase III trial, in which Jardiance significantly reduced the risk of kidney disease progression* or cardiovascular death in adults with CKD by 28% (ARR: 3.8%) compared with placebo, both on top of standard of care. Results were presented during the American Society of Nephrology (ASN)'s Kidney Week 2022 and simultaneously published in The New England Journal of Medicine. EMPA-KIDNEY is the first SGLT2 inhibitor CKD trial to show a significant reduction in risk of hospitalization for any cause, with a 14% relative risk reduction with Jardiance versus placebo (24.8 vs. 29.2 events/100 patient-years, respectively), both on top of standard of care, in a pre-specified key secondary endpoint. Reductions in other key secondary endpoints of hospitalization for heart failure or cardiovascular death or all-cause death were not statistically significant. Hospitalizations account for 35% to 55% of total healthcare costs for people with CKD in the U.S.

EMPA-KIDNEY, the largest and broadest dedicated SGLT2 inhibitor trial in CKD to date, provides additional data for patients commonly seen in clinical practice. The trial enrolled 6,609 participants, including people without diabetes (56%), those with various underlying causes of CKD and those across the spectrum of eGFR and urine albumin-creatinine ratio (measures of kidney function and excess albumin in the urine, respectively). Overall, the safety data in EMPA-KIDNEY were consistent with the previously known safety profile of Jardiance.

Initially approved in 2014, Jardiance is a once-daily tablet used along with diet and exercise to lower blood sugar in adults with type 2 diabetes; and to reduce the risk of cardiovascular death in adults with type 2 diabetes and known cardiovascular disease. Jardiance is also indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure. Jardiance is not for patients with type 1 diabetes, or to improve glycemic control in adults with type 2 diabetes with an eGFR <30 mL/min/1.73 m2. Jardiance is contraindicated in people with hypersensitivity to empagliflozin or any of the excipients in Jardiance, and in patients on dialysis. Please see additional Important Safety Information below.

"This marks another exciting milestone for Jardiance, potentially extending its ability to positively impact the approximately one billion people diagnosed with a cardio, renal or metabolic condition," said Jeff Emmick, M.D., Ph.D., vice president, Product Development, Lilly. "We look forward to working with the FDA during the review process and eagerly await a decision later this year on the indication for CKD, which doubles a person's risk for hospitalization."

In March 2020, the FDA granted Fast Track designation to the clinical investigation of Jardiance to reduce the risk of kidney disease progression and cardiovascular death in adults with CKD. According to the FDA, Fast Track designation is designed to facilitate the development of drugs and expedite treatments that may address serious conditions and fill an unmet medical need. Jardiance is not indicated for the treatment of CKD.

*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: The study of heart and kidney protection with Jardiance

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 percent 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 randomized from eight countries with established CKD both with and without diabetes, as well as with and without albuminuria, receiving either Jardiance 10 mg or placebo, on top of current standard of care.

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 cardiovascular death in adults with type 2 diabetes who also have known cardiovascular disease

• lower blood sugar along with diet and exercise in adults with type 2 diabetes

JARDIANCE is not for 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 adults with type 2 diabetes who have severe kidney problems, because it may not work.