EU Okays CV Benefit Labeling for Canagliflozin in Diabetes

Miriam E. Tucker

September 21, 2018

The European Commission has granted approval for the addition of positive cardiovascular outcomes data on the label of the SGLT2 inhibitor canagliflozin (Invokana, Vokanamet, Janssen).

Inclusion of the data, from the company's CANVAS clinical trial program, will allow the drug to be marketed for the prevention of major cardiovascular events (cardiovascular death, nonfatal myocardial infarction, and stroke) in addition to glucose-lowering for adults with type 2 diabetes and a history of cardiovascular disease or at least two cardiovascular risk factors.

Canagliflozin was first approved in the European Union for the treatment of insufficiently controlled type 2 diabetes in November 2013.

In the Canagliflozin Cardiovascular Assessment Study (CANVAS) , which involved more than 10,000 patients with type 2 diabetes with a history or at risk of cardiovascular events, canagliflozin reduced the risk of major cardiovascular adverse events by 23 events/1000 patients over 5 years, hospitalization for heart failure by 17 events/1000 patients, and renal events by 16 events/1000 patients.

However, the drug was also associated with a two-fold increased risk for amputations, from 0.34 to 0.63/100 patient-years. A warning about the amputation risk is already included in the European labeling of all drugs in the SGLT2 inhibitor class. In the United States, the same warning is listed only on the canagliflozin label.

In much of Europe, canagliflozin is distributed by Mundipharma.

Canagliflozin is the second SGLT2 inhibitor to have the cardiovascular benefit acknowledged in its label. Empagliflozin (Jardiance, Lilly/Boehringer Ingelheim) already has an indication for reducing cardiovascular death in addition to improving glycemic control in patients with type 2 diabetes both in the European Union and United States.

Another type 2 diabetes drug, liraglutide (Victoza, Novo Nordisk), a subcutaneous injectable glucagonlike peptide 1 (GLP-1) agonist, also has an indication for reducing the risk of cardiovascular events in patients with type 2 diabetes at high risk, again, both in the United States and European Union.

The demonstration of cardiovascular benefit for some newer type 2 diabetes drugs has prompted the American Diabetes Association and European Association for the Study of Diabetes to indicate in a joint consensus statement that they plan to recommend a new approach to the treatment of type 2 diabetes, which should begin with an assessment of cardiovascular disease status and other comorbidities.

US Status of Canagliflozin

In July of this year, the US Food and Drug Administration (FDA) extended its review timeline of Janssen's request for the supplemental new drug application for inclusion of reduction of major cardiovascular events in canagliflozin’s label.

A decision is expected in October.

Canagliflozin was first approved by the FDA in March 2013 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. In 2017, following the interim CANVAS data, the agency required the addition of the boxed warning about the amputation risk.

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