New Real-World Analysis Shows INVOKANA® (canagliflozin) and Other SGLT2 Inhibitors Reduced the Risk of Death and Cardiovascular Events Compared to Other Diabetes Medicines

TITUSVILLE, N.J., Nov. 17, 2017 — A new real-world analysis of adults with type 2 diabetes and established cardiovascular disease (CVD) shows adult patients who initiated therapy with INVOKANA^® (canagliflozin) or another sodium glucose cotransporter-2 inhibitor (SGLT2i) had a 43 percent reduced risk for all-cause mortality (ACM) and hospitalization for heart failure (HHF) after an average of 1.6 years, compared to similar patients who initiated treatment with a non-SGLT2i medication using an intent-to-treat (ITT) approach. Additionally, patients who initiated SGLT2i therapy had a 33 percent reduced risk of major adverse cardiovascular events (MACE), including ACM, non-fatal myocardial infarction (MI) and non-fatal stroke. This new retrospective analysis from the EASEL (Evidence for cArdiovascular outcomes with Sodium glucose co-transporter 2 inhibitors in the rEal worLd) study is based on data from the U.S. Department of Defense Military Health System and was published this week in Circulation.

"This is the first real-world study to demonstrate a lower risk of MACE in patients with type 2 diabetes and established CVD who were initiated on SGLT2i therapy," said Paul Burton, MD, PhD, FACC, Vice President, Medical Affairs, Janssen. "These results further reinforce the positive effects of INVOKANA^®and SGLT2is in cardiovascular risk reduction."

Study and Findings
The population-based EASEL study included two cohorts: 12,629 new users of a SGLT2i and 12,629 new users of a non-SGLT2i diabetes medication, both on top of standard-of-care therapy. The two cohorts were matched on propensity scores, with a model including various characteristics such as demographics, duration of diabetes, baseline comorbidities and medication use, diagnoses and procedures, and various health care resource utilization measures. In the SGLT2i cohort, canagliflozin, empagliflozin and dapagliflozin accounted for 58.1 percent, 26.4 percent and 15.5 percent of patients, respectively. The median follow-up for the two cohorts was 1.6 years based on the ITT approach.

The primary outcome was the composite of ACM and HHF. Several other CVD-related events were also assessed as secondary endpoints. The ITT analysis showed that the SGLT2i cohort had statistically significant reductions in the incidence of multiple endpoints compared to the non-SGLT2i cohort, respectively, including:

• 43 percent reduction in the composite outcome of ACM and HHF (primary endpoint): 1.73 vs. 3.01 events per 100 person-years; hazard ratio (HR) 0.57, 95 percent confidence interval (CI): 0.50-0.65; P <0.0001.
• 43 percent reduction in ACM (secondary endpoint): 1.29 vs. 2.26 events per 100 person-years; HR 0.57, CI: 0.49-0.66; P <0.0001.
• 43 percent reduction in HHF (secondary endpoint): 0.51 vs. 0.90 events per 100 person-years; HR 0.57, CI: 0.45-0.73; P <0.0001.
• 33 percent reduction in MACE (secondary endpoint): 2.31 vs. 3.45 events per 100 person-years; HR 0.67, CI: 0.60-0.75; P <0.0001. The rate of the individual endpoints of non-fatal MI and non-fatal stroke were not significantly different between the two cohorts.
• 34 percent reduction in the composite of MACE and HHF (secondary endpoint): 2.72 vs. 4.11 events per 100 person-years; HR 0.66, CI: 0.60-0.74; P <0.0001.

The incidence rate of below-knee lower extremity amputation (BKA) in the SGLT2i cohort was relatively infrequent — approximately two-fold compared to the non-SGLT2i cohort: 35 vs. 18 events (0.17 vs. 0.09 events per 100 person-years, HR 1.99, CI: 1.12-3.51; P=0.018). It remains unclear whether the BKA risk extends across the SGLT2i class of medications as the study was not powered to make comparisons among individual treatments.

Of the approximately 30 million people living with diabetes in the United States, 90 to 95 percent have type 2 diabetes, and are two to four times more likely to die from heart disease than those without diabetes.

One of the largest public health insurance claims programs in the United States, the Department of Defense Military Health System (MHS) includes active or retired service members and their dependents, with close to 10 million patients actively receiving care. The database integrates all medical, clinical, pharmacy and administrative data for every eligible MHS beneficiary across the United States.

INVOKANA^® (canagliflozin) is indicated as an adjunct to diet and exercise to lower blood sugar in adults with type 2 diabetes. It is not indicated to reduce the risk of ACM, HHF or MACE, which includes ACM, non-fatal MI and non-fatal stroke. The landmark CANVAS Program, the largest completed CV outcomes program to date, evaluated the cardiovascular safety and efficacy of canagliflozin relative to placebo in adults with type 2 diabetes who had either established CVD or were at risk for CVD. A supplemental new drug application (sNDA) based on data from the CANVAS Program was filed with the FDA on October 2, 2017.

WHAT IS INVOKANA^®?
INVOKANA^® (canagliflozin) is a prescription medicine used along with diet and exercise to lower blood sugar in adults with type 2 diabetes. INVOKANA^® is not for people with type 1 diabetes or with diabetic ketoacidosis (increased ketones in blood or urine). It is not known if INVOKANA^® is safe and effective in children under 18 years of age.