EU backs Canagliflozin to slow diabetic kidney disease
A recommendation for approval has been made for the sodium-glucose cotransporter 2 (SGLT2) inhibitor canaglifozin (Invokana, Janssen) to be extended to include the treatment of diabetic kidney disease.
The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion to extend the indication of canagliflozin to include important renal outcome data from the landmark Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial.
It is already marketed for type 2 diabetes. If approved by the European Commission, canagliflozin will be the first therapy approved in nearly 20 years, since the approval of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), to slow the progression of diabetic kidney disease (DKD) among people with type 2 diabetes, including those with moderate and severe renal impairment.
Dr Ogün Sazova, Napp Medical Director, said: “The CHMP positive opinion is exciting news and highlights how diabetic kidney disease has become an integral part of type 2 diabetes management. The opinion to extend the label to include patients who are likely to need renal replacement therapy means that Invokana will be available to slow the progression of diabetic kidney disease in this additional population of people with type 2 diabetes.”
The CREDENCE trial is the first dedicated and published renal outcomes study in people with DKD and type 2 diabetes. The study enrolled 4,401 subjects with an eGFR of 30 to <90ml/min/1.73m and albuminuria (urinary albumin: creatinine ratio >300 to 5000 mg/g).
All participants were treated on a background of standard of care for DKD, including angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (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]: 0.59 to 0.82; p<0.00001).
Rates of adverse events and serious adverse events were similar overall in the canagliflozin group and the placebo group. There were no observed differences in the incidence of lower limb amputations (12.3 vs 11.2 events per 1000 patient years; HR: 1.11; 95% CI: 0.79 to 1.56) or adjudicated bone fractures (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.
In the UK, canagliflozin is currently indicated for the treatment of adults with insufficiently controlled type 2 diabetes and an eGFR of ≥60 mL/min/1.73 m2, as an adjunct to diet and exercise, as monotherapy when metformin is considered inappropriate due to intolerance or contraindications and in addition to other medicinal products for the treatment of diabetes.