European Commission approves Invokana to treat diabetic kidney disease (DKD) in type 2 diabetes. – Mundipharma.

Mundipharma announces that the European Commission (EC) has approved the extension of the indication of Invokana (canagliflozin) to include important renal outcome data from the landmark Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial. Canagliflozin is now the only sodium glucose co-transporter 2 inhibitor (SGLT2i) approved in Europe with an extended indication to treat diabetic kidney disease (DKD) in type 2 diabetes (T2DM) patients.

For the first time in Europe, T2DM patients with an estimated glomerular filtration rate (eGFR) between 60 and 45 mL/min/1.73m2 can now initiate treatment with canagliflozin 100mg. In addition, T2DM patients with albuminuria and an eGFR greater than 30 mL/min/1.73m2 can now start treatment with canagliflozin 100mg and continue until dialysis or renal transplantation.

The CREDENCE trial is the first dedicated renal outcomes study in patients with DKD and T2DM . The study enrolled 4401 subjects with an eGFR of 30 to 300 to 5000 mg/g). Importantly, all patients were treated on a background of standard of care for DKD, including a maximum tolerated dose of an ACE inhibitor or ARB. The results showed that canagliflozin demonstrated a 30% reduction, compared to placebo, in the risk of the primary composite endpoint, comprising end-stage renal disease (ESRD), doubling of serum creatinine and renal or cardiovascular (CV) death, with event rates of 43.2 vs 61.2 per 1000 patient years, respectively (Hazard Ratio [HR]: 0.70; 95% Confidence Interval [CI]: 0.57 to 0.84; p<0.0001).

Rates of adverse events and serious adverse events were similar overall in the canagliflozin group and the placebo group. There were no statistical differences in the incidence of lower limb amputations (canagliflozin 12.3 vs placebo 11.2 events per 1000 patient years; HR: 1.11; 95% CI: 0.79 to 1.56) or adjudicated bone fractures (canagliflozin 11.8 vs 12.1 events per 1000 patient years; HR: 0.98; 95% CI: 0.70 to 1.37). The study was stopped early in July 2018, owing to positive efficacy finding.