Late-breaking study shows improved renal and heart failure outcomes also seen with INVOKANA® in both of these patient groups

RARITAN, NJ and ANAHEIM, CA, USA I November 14, 2017 I Janssen Research & Development, LLC (Janssen) today announced a new analysis from the CANVAS Program, which showed INVOKANA® (canagliflozin) demonstrated a reduced risk of cardiovascular (CV) outcomes in patients with and without a history of CV disease. INVOKANA® also achieved similar and proportional risk reductions for hospitalization due to heart failure (HHF) and renal outcomes in each of the primary and secondary prevention groups. These late-breaking results were presented at the American Heart Association (AHA) Scientific Sessions 2017 in Anaheim, California on November 13 and simultaneously published in Circulation.

This analysis of CANVAS examined two high-CV-risk type 2 diabetes patient groups: those with a history of CV disease (secondary prevention) and those with only risk factors for CV disease (primary prevention). In this analysis, both patient groups showed CV outcomes consistent with the overall reduction seen in CV events: primary (HR: 0.98; 95% CI: 0.74 to 1.30) and secondary (HR: 0.82; 95% CI: 0.72 to 0.95), with no statistical evidence of between-group heterogeneity (p = 0.18). Comparable effects were also observed for other CV and renal outcomes across the primary and secondary prevention groups.

As previously reported, in the total cohort of the CANVAS Program, canagliflozin reduced the combined risk of CV death, nonfatal myocardial infarction (MI) and nonfatal stroke by 14 percent, compared to placebo (HR: 0.86; 95% CI: 0.75 to 0.97, p=0.0158).

“All people with type 2 diabetes have an increased risk of developing cardiovascular and renal diseases,” said James F. List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular & Metabolism, Janssen. “This new CANVAS analysis is clinically important, because it shows that INVOKANA® may offer a broad range of patients an effective treatment option to reduce their risk of cardiovascular and renal disease.”

This new analysis also found:

  • Patients with prior CV events had an overall greater primary endpoint event rate compared to those who had two or more CV risk factors (36.9 vs 15.7/1000 patient-years; p <0.001)
  • INVOKANA® lowered the risk of HHF in both patient groups: primary (HR: 0.64; 95% CI: 0.35 to 1.15) with interaction p = 0.91 and secondary (HR: 0.68; 95% CI: 0.51 to 0.90)
  • INVOKANA® achieved a reduction in the risk of the composite renal endpoint in both patient groups: primary (HR: 0.63; 95% CI: 0.39-1.02) and secondary (HR: 0.59, 95% CI: 0.44-0.79) with interaction p = 0.73
  • The overall adverse event profile for canagliflozin compared with placebo was consistent in the primary and secondary prevention participants (p interactions all >0.07)
  • No new adverse events were observed during this additional analysis than what was previously reported from the CANVAS Program

The primary prevention cohort was comprised of individuals aged ≥50 years with at least two risk factors for CV events; the secondary prevention cohort was comprised of individuals aged ≥30 years with a prior CV event. Primary prevention participants (N=3486; 34%) were younger (63 vs 64 years), more often female (45% vs 31%), and had longer duration of diabetes (14 vs 13 years) compared to secondary prevention participants (N=6656; 66%). 

Data from the integrated analysis of the CANVAS and CANVAS-R trials were presented in a special symposium at the American Diabetes Association 77th Scientific Sessions on June 12 in San Diego, CA, and simultaneously published in The New England Journal of Medicine.

Notably, the ongoing, fully enrolled CREDENCE Program – the first dedicated SGLT2 inhibitor Phase 3 renal outcomes trial – is further evaluating the effects of canagliflozin on renal outcomes in patients with T2DM and kidney disease.

About the CANVAS Program

The CANVAS Program is the longest, largest and broadest completed CV outcomes program of any sodium glucose cotransporter-2 (SGLT2) inhibitor to date and is composed of two nearly-identical large outcomes studies: CANVAS (CANagliflozin CardioVascular Assessment Study (NCT01032629) and CANVAS-R (Study of the Effects of Canagliflozin on Renal Endpoints in Adult Subjects with T2DM, (NCT01989754).

The Program evaluated a total of 10,142 patients – 4,330 patients in CANVAS and 5,812 patients in CANVAS-R. In the randomized, placebo-controlled Phase 3/4 studies, a vast majority of patients were obese, with a history of hypertension, 66 percent of patients had a history of CV disease (14 percent had a history of heart failure), and 34% of patients had at least two CV risk factors. The study assessed the safety of canagliflozin relative to placebo in patients receiving specific commonly-used diabetes agents. The primary endpoint was defined as major adverse CV events (MACE), composed of nonfatal MI, nonfatal stroke, and CV death, and the secondary endpoint was defined as progression of albuminuria, beta-cell function, estimated glomerular filtration rate (eGFR) changes and urine albumin-to-creatinine ratio (UACR).

In the CANVAS study, patients were randomly assigned in a 1:1:1 ratio to placebo, canagliflozin 100mg and canagliflozin 300mg. The mean and median exposure to investigational product was approximately 4.3 and 5.8 years, respectively. The mean and median follow-up time was 5.7 and 6.1 years, respectively.

In the CANVAS-R study, patients were randomly assigned in a 1:1 ratio to placebo or canagliflozin 100mg (with an investigator option to up-titrate to 300mg if the patient required additional glycemic control, provided the 100mg dosage was well tolerated). The mean and median exposure to investigational product was approximately 1.8 and 1.9 years, respectively. The mean and median follow-up time was 2.1 years.

These CANVAS and CANVAS-R studies were designed to be highly similar in patient population, procedures and assessments, evaluating the effects of canagliflozin on CV events in a similar study population. This approach is demonstrated in three published studies: “Rationale, design, and baseline characteristics of the Canagliflozin Cardiovascular Assessment Study (CANVAS)—A randomized placebo-controlled trial,” published online by American Heart Journal; “Rationale, design and baseline characteristics of the CANagliflozin cardioVascular Assessment Study–Renal (CANVAS-R): A randomized, placebo-controlled trial,” published online by Diabetes, Obesity and Metabolism; and “Optimizing the analysis strategy for the CANVAS Program – a pre-specified plan for the integrated analyses of the CANVAS and CANVAS-R trials,” published online by Diabetes, Obesity and Metabolism.

About INVOKANA®

In March 2013, the U.S. FDA approved canagliflozin – INVOKANA® – as a single agent. In two studies comparing INVOKANA® plus metformin to current standard treatments plus metformin – one studying sitagliptin1 and the other studying glimepiride2 – INVOKANA® dosed at 300 mg provided greater reductions in A1C levels and body weight than either comparator. In the two studies, the overall incidence of adverse events was similar with INVOKANA® and the comparators. INVOKANA® continues to be the number-one prescribed SGLT2 inhibitor. Since its launch, more than 16 million prescriptions have been written for INVOKANA® in the U.S.*

WHAT IS INVOKANA®?

INVOKANA® 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.

Please see full Product Information, including Boxed Warning, and Medication Guide for INVOKANA®.

Canagliflozin is licensed from Mitsubishi Tanabe Pharma Corporation.

Trademarks are those of their respective owners.

About the Janssen Pharmaceutical Companies

At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science. We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com. Follow us at @JanssenUS.

*YTD TRx Volumes in 2017. IMS NPA weekly data through 10/20/17

1 Lavalle-Gonzalez F, Januszewicz A, Davidson J, et al. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia. 2013 Dec;56(12):2582-92.
2 Cefalu T, Leiter L, Yoon K-H, Arias P, Niskanen L, Xie J, Balis D, Canovatchel W, Meininger G. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet. 2013 Sep 14;382(9896):941-50.

SOURCE: Janssen