CANVAS study shows Invokana improves outcomes in type 2 diabetes with CV risk.- Janssen R&D.

Janssen Research & Development announced additional analyses from the landmark CANVAS clinical trial program showing Invokana (canagliflozin) improved renal outcomes and demonstrated potential renal protective effects in patients with type 2 diabetes mellitus (T2DM), who either have, or are at risk for, cardiovascular (CV) disease. The renal analyses showed that compared to placebo, canagliflozin reduced the risk of kidney disease progression, including significantly reducing urinary albumin excretion and stabilizing estimated glomerular filtration rate (eGFR) over a study duration of more than six years.

Canagliflozin reduced the rates of several pre-specified major renal composite endpoints by up to 47 percent, such as end-stage kidney disease (ESKD), doubled serum creatinine (dSCr) or renal death. Urinary albumin excretion was 18 percent lower in all participants treated with canagliflozin compared with placebo. It was 34 percent lower in participants with baseline microalbuminuria and 36 percent lower in those participants with baseline macroalbuminuria. Median urinary albumin to creatinine ratio (UACR) was 12.3 mg/g. Participants treated with canagliflozin experienced an initial decline in mean eGFR; thereafter, that rate gradually increased over the study duration (6.5 years).

In contrast, participants treated with placebo experienced a progressive decline in eGFR. Mean baseline eGFR was 76.5 mL/min/1.73 m2. There was no increase in renal adverse events (serious or non-serious) compared to placebo, including acute kidney injury and hyperkalemia. Invokana demonstrated consistent improvement of renal outcomes across multiple composite endpoints that were independently confirmed by an Endpoints Adjudication Committee. These data were presented at the American Society of Nephrology (ASN) Kidney Week 2017 Annual Meeting.

Comment: The ongoing, fully enrolled CREDENCE trial, the first dedicated SGLT2 inhibitor Phase III renal outcomes trial, is evaluating the effects of canagliflozin on renal outcomes in patients with T2DM and kidney disease.