Therapy Areas: Cardiovascular
Janssen Receives Positive CHMP Opinion to Expand Invokana and Vokanamet Labelling to Include Positive Data on Cardiovascular Morbidity and Mortality
3 August 2018 - - The Committee for Medicinal Products for Human Use, of the European Medicines Agency, has issued a positive opinion to update the Invokana (canagliflozin) and Vokanamet (canagliflozin and metformin) labelling including changes to the indication statement for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise, US-based healthcare company Johnson and Johnson's (NYSE: JNJ) The Janssen Pharmaceutical Companies business said.

According to the company, the recommended product information now includes data on the reduction in major adverse cardiovascular events (cardiovascular mortality, non-fatal myocardial infarction, or non-fatal stroke) in patients with type 2 diabetes mellitus who had either a history of CV disease or at least two CV risk factors, in addition to the existing study results on improving glycemic control.

The CHMP's positive opinion will now be reviewed by the European Commission, which has the authority to grant approval of the updated label.

The Type II variation application is based on the results of the CANVAS Program, the largest completed CV outcomes trial to date for an SGLT2 inhibitor. 

The study, which included over 10,000 patients started in 2009, met its primary endpoint and showed canagliflozin significantly reduced the combined risk of CV death, myocardial infarction and non-fatal stroke, versus placebo in adult patients with T2DM who had either a history of CV disease or at least two CV risk factors.

Canagliflozin also significantly lowered the risk of hospitalization for heart failure and demonstrated improved renal outcomes.

Adverse events reported in the CANVAS Program were generally consistent with the known safety profile of canagliflozin.

However, the study found that, in patients with T2DM who had established CV disease or at least two risk factors for CV disease, canagliflozin was associated with an approximately 2-fold increased risk of lower limb amputation with the rate of amputation over standard of care being 0.63/100 patient years for canagliflozin versus 0.34/100 patient years for placebo which corresponds to an additional risk of 0.29/100 patient years.

The risk of amputations across the class has previously been investigated by the EMA, and this is reflected in a warning in the labelling of SGLT2 inhibitors.

Canagliflozin was approved in the European Union by the European Commission in November 2013 and is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus.

Approval was based on a comprehensive global Phase 3 clinical trial programme.

Janssen has a partnership with Mundipharma, who is the exclusive distributor for both Invokana and Vokanamet in countries in the European Economic Area and Switzerland where the products currently have pricing and reimbursement status.

Mundipharma has exclusive rights to promote, distribute, and sell both products through its network of independent associated companies.

This is with the exception of Spain, where the product is co-promoted by both Janssen and Mundipharma.

The CANVAS Program (N=10,142) comprises the two large canagliflozin CV outcome studies, CANVAS and CANVAS-R, and includes a pre-specified integrated analysis of these two studies to evaluate the potential for CV protection of canagliflozin in patients with T2DM who had either a prior history of CV disease or at least two CV risk factors.

The integrated analysis also evaluated the effects of canagliflozin on renal and safety outcomes.

Canagliflozin met the primary outcome by significantly reducing the rates of the composite of major adverse CV events comprised of CV mortality, non-fatal myocardial infarction, or non-fatal stroke (26.9 vs. 31.5/1000 patient-years, hazard ratio 0.86; 95% confidence interval (CI 0.75-0.97; P


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