CANVAS program results for Invokana (canagliflozin) show improvement in CV outcomes in type 2 diabetes patients.- Johnson & Johnson

Results from the landmark CANVAS Program showed Invokana (canagliflozin) from Johnson & Johnson, significantly reduced the combined risk of cardiovascular (CV) death, myocardial infarction (MI), and nonfatal stroke, versus placebo in patients with type 2 diabetes mellitus (T2DM) at risk for or with a history of CV disease. The results also showed canagliflozin treatment was associated with a reduced risk for hospitalization for heart failure (HHF) and demonstrated potential renal protective effects. These data from the integrated analysis of the CANVAS and CANVAS-R trials were published in the New England Journal of Medicine and presented in a special symposium at the American Diabetes Association 77th Scientific Sessions on Monday,12 June in San Diego.

Canagliflozin was studied in the longest, largest and broadest completed CV outcomes program of any sodium glucose cotransporter-2 (SGLT2) inhibitor. The CANVAS Program is the first program to assess the efficacy, safety, and durability of canagliflozin in more than 10,000 patients with T2DM, who had either a prior history of CV disease, or at least two CV risk factors. Canagliflozin achieved a 14% reduction in the risk of the composite primary endpoint of CV mortality, nonfatal MI or nonfatal stroke (HR: 0.86; 95% CI: 0.75 to 0.97), and demonstrated the CV safety of canagliflozin (p<0.0001 for non-inferiority) and superiority compared to placebo (p=0.0158). Each component evenly contributed to this risk reduction, including nonfatal MI by 15% (HR: 0.85; 95% CI: 0.69 to 1.05), CV death by 13% (HR: 0.87; 95% CI: 0.72 to 1.06), and nonfatal stroke by 10% (HR: 0.90; 95% CI: 0.71 to 1.15). These outcomes were broadly consistent across various patient subgroups and across the individual components of the primary endpoint. Additional analysis further revealed canagliflozin lowered the risk of heart failure by 33% (HR: 0.67; 95% CI: 0.52 to 0.87) and provided sustained positive effects on glycemic and blood pressure control, as well as weight reduction, demonstrating wide-ranging durability. In addition, canagliflozin showed potential renal protective effects, delaying progression of albuminuria and reducing the risk of clinically important renal composite outcomes (such as renal death, renal replacement therapy, and 40% reduction of eGFR) by 40% (HR: 0.60; 95% CI: 0.47 to 0.77).

The ongoing, fully enrolled CREDENCE study, the first dedicated SGLT2 inhibitor renal outcome trial in patients with T2DM and kidney disease, is further evaluating the effects of canagliflozin on renal and CV outcomes.

Overall adverse events seen in the CANVAS Program were consistent with previous findings. An increased risk of amputation with canagliflozin was seen in both the completed CANVAS study and CANVAS-R studies.

Comment: The reduction of composite CV risk was 14% which was the same as for Jardiance from Eli Lilly + Boehringer. Invokana reduced the rate of heart attack and stroke by 15% and 10% respectively whereas Jardiance failed to make a significant difference to these factors. Invokana reduced the risk of CV death by 13% compared to the reduction achieved by Jardiance of 38% . Invokana carried a twofold increase in lower extremity amputations, a feature that is now reflected as a warning in its label.

See- "Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes"- Bruce Neal, M.B., Ch.B., Ph.D., Vlado Perkovic, M.B., B.S., Ph.D., et al., for the CANVAS Program Collaborative Group June 12, 2017DOI: 10.1056/NEJMoa1611925.