European Commission approves extended Invokana ® (canagliflozin) indication

Image of a contract being signed by two people with a certification stamp to show European Commission approves extended Invokana ® (canagliflozin) indication

The European Commission has approved an extended Invokana ® (canagliflozin) indication to reflect improved renal outcomes in patients with diabetic kidney disease and type 2 diabetes seen in CREDENCE study.

Mundipharma has announced 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 ≥30 mL/min/1.73m2 can now start treatment with canagliflozin 100mg and continue until dialysis or renal transplantation.

“We are delighted with this extended indication granted by the European Commission, which means that patients with T2DM and kidney complications now have a new treatment option to help reduce their risk of developing kidney failure, thus potentially reducing the need for dialysis or kidney transplantation.“ said Dr Vinicius Gomes de Lima, European Medical Affairs Lead, Mundipharma. “The European Medicines Agency has reinforced that management of DKD should be a key treatment goal of type 2 diabetes and it is therefore crucial that physicians have effective treatments to help stop the progression of this life-threatening complication.”

Professor Vlado Perkovic, Study Author and Professorial Fellow at the George Institute, Australia, Dean of Medicine at UNSW Sydney commented: “Canagliflozin is the first medical breakthrough in nearly 20 years proven to slow the progression of chronic kidney disease in patients with diabetes at high risk of developing kidney failure. These impressive results from the CREDENCE study have significant clinical implications for preventing kidney failure and have now been incorporated in major kidney, diabetes and cardiovascular guidelines globally. They provide an opportunity to significantly improve the health of millions of people living with chronic kidney disease and type 2 diabetes. With the new approval by The European Commission, these benefits can be realised by people across Europe.”

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 <90ml/min/1.73m2 and albuminuria (urinary albumin: creatinine ratio >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 findings.

Canagliflozin has been approved in the European Union since 2013, where it is indicated for the treatment of adults with insufficiently controlled T2DM as an adjunct to diet and exercise, either as monotherapy or in addition to other blood sugar-reducing medicinal products. Full prescribing information.

As commercial partner to Janssen Pharmaceutica NV, Mundipharma has exclusive distribution rights for canagliflozin in various countries within Europe.