Janssen: Invokana significantly cuts risk of CV death, heart attack, stroke
Johnson & Johnson's Janssen announced that results from the landmark CANVAS Program showed INVOKANA significantly reduced the combined risk of cardiovascular death, myocardial infarction, and nonfatal stroke, versus placebo in patients with type 2 diabetes mellitus 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 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 at the American Diabetes Association annual meeting. Specifically, canagliflozin achieved a 14% reduction in the risk of the composite primary endpoint of CV mortality, nonfatal MI or nonfatal stroke, and demonstrated the CV safety of canagliflozin and superiority compared to placebo. Each component evenly contributed to this risk reduction, including nonfatal MI by 15%, CV death by 13%, and nonfatal stroke by 10%. 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 HHF by 33% 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 by 40%. 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 and CANVAS-R studies. There was an increased risk of amputation corresponding to a hazard ratio of 1.97. The highest absolute risk of amputation occurred in patients with a prior history of amputation or peripheral vascular disease, but the relative risk for amputation with canagliflozin was comparable across these subgroups. These findings have been shared by the U.S. FDA and will be reflected in the U.S. Prescribing Information for canagliflozin, the company noted. Separately, while an increased risk of adjudicated low trauma fracture was identified in the CANVAS study, no increase was observed in the CANVAS-R study. A full assessment is ongoing to provide a complete safety review of these results.