J&J's Invokana improves CV outcomes despite amputation risk

Johnson & Johnson (NYSE:JNJ) reported pooled data from the double-blind, international Phase III CANVAS and Phase IV CANVAS-R trials in a total of 10,142 Type II diabetics at high cardiovascular (CV) risk showing that Invokana canagliflozin (TA-7284, JNJ-28431754) met the primary endpoint of reducing a composite of CV death, non-fatal myocardial infarction (MI) and non-fatal stroke vs. placebo (26.9 vs. 31.5 patients with an event per 1,000 patient-years, HR=0.86, 95% CI: 0.75, 0.97, p<0.0001 for non-inferiority and p=0.0158 for superiority). Invokana did lead to a higher incidence of amputation of toes, feet or legs vs. placebo (6.3 vs. 3.4 patients with amputation per 1,000 patient-years, HR=1.97, 95% CI: 1.41, 2.75). J&J said the amputation risk was consistent with prior data and will be reflected in U.S. prescribing information and has already been included in the drug’s EU Summary of Product Characteristics. Data were presented at the American Diabetes Association meeting in San Diego and published in the New England Journal of Medicine.

J&J was forced to run CANVAS-R after FDA determined that data from CANVAS alone were no longer sufficient to fulfill Invokana's postmarketing requirements. The agency was concerned that disclosure of interim data from CANVAS may have compromised its results...