Regulatory Decision Summary for Jardiance

This Supplement to a New Drug Submission was filed to obtain market authorization for a new indication for Jardiance to treat chronic kidney disease in adults.

EMPA-KIDNEY was an international, multicenter, randomized, double-blind, placebo-controlled trial in adult chronic kidney disease (CKD) patients with baseline estimated glomerular filtration rate (eGFR) greater than or equal to 20 and less than 45 millilitres per minute per 1.73 square metres (mL/min/1.73m²), or eGFR ≥45 to <90 mL/min/1.73m² with urine albumin to creatinine ratio (UACR) greater than or equal to 200 milligrams per gram (mg/g). A total of 6,609 CKD patients were randomised to either Jardiance 10 milligrams (mg) (n = 3,304) or placebo (n = 3,305) once daily treatment in addition to standard of care therapy, and followed for a median of 24.3 months (median exposure to study medication 22 months). Approximately 44.4% (n = 2,936) of the patients had type 2 diabetes mellitus (T2DM). The primary efficacy endpoint was a composite of the time to the first occurrence of kidney disease progression or cardiovascular (CV) death. The kidney disease progression was defined as sustained decline of greater than or equal to 40% in eGFR, sustained decline in eGFR to less than10 mL/min/1. 73 m², end-stage kidney disease (ESKD), or renal death.

Jardiance treatment reduced the incidence of the primary composite endpoint by 28% compared to placebo (Hazard Ratio 0.72 [95% Confidence Interval 0.64, 0.82], probability <0.0001). The treatment benefits of Jardiance demonstrated on the primary composite endpoint were generally consistent in CKD patients with and without T2DM, across subgroups defined by baseline eGFR, baseline UACR, underlying cause of renal disease, background use of renin–angiotensin system (RAS) inhibitors, age, sex, race, or region.

The safety results of EMPA-KIDNEY were generally consistent with the known safety profile of Jardiance in prior T2DM and heart failure trials. In total, 3,304 CKD patients were exposed to Jardiance 10 mg once daily for a median of 22 months, with 91% of participants treated for at least 1 year and 44% for at least 2 years. There were slightly fewer patients who had serious adverse events (SAEs) in the Jardiance group (32.9%) than in the placebo group (35.3%). The numbers of patients who prematurely discontinued treatment due to an adverse event (AE) were similar in Jardiance (7.0%) and placebo (7.3%) groups. Ketoacidosis occurred in 6 patients in the Jardiance group and in 1 patient in the placebo group (0.10 and 0.02 per 100 patient years, respectively). Although most of the ketoacidosis events occurred in patients with diabetes, ketoacidosis was reported in one non-diabetic patient in the Jardiance group. AEs of volume depletion were reported in 98 (3.0%) patients in the Jardiance group and 90 (2.7%) in the placebo group. SAEs of volume depletion were reported in 46 (1.4%) patients in the Jardiance group and 41 (1.2%) patients in the placebo group. More symptomatic dehydration events were observed in the Jardiance group (2.4%) than the placebo (2.1%). The occurrence of lower limb amputation (LLA) was reported in 28 (0.8%) patients in Jardiance group and 19 (0.6%) patients in placebo, respectively, with toe amputation most commonly reported in both groups. A numerically higher incidence of LLA was observed in the Jardiance group regardless of diabetes status, although most LLAs occurred in the CKD patients with T2DM. The overall frequencies for liver injury, serious urinary tract infection, serious genital infection, severe hypoglycaemia, serious hyperkalemia, and urinary tract malignancy were comparable between the Jardiance and placebo group.

Data for initiating Jardiance treatment in patients with baseline eGFR below 20 mL/min/1.73m² remains unknown.

A Risk Management Plan was reviewed by the Marketed Health Products Directorate and was considered acceptable.

Overall, the benefit-harm-uncertainty assessment of Jardiance is considered favorable for the treatment of CKD in adults to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular and renal death.

For further details about Jardiance, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.