Regulatory Decision Summary for Victoza
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
Type of submission:
What was the purpose of this submission?
The purpose of this submission was to rule out an increased risk of cardiovascular disease in patients taking Victoza. Novo Nordisk was to conduct a controlled trial evaluating the effect of Victoza on the development of major cardiovascular side-effects (e.g., cardiovascular death, heart attack, or stroke) in adult patients with type 2 diabetes mellitus (T2D). Since patients with T2D are already at risk for cardiovascular disease due to diabetes, it is important that anti-diabetic therapies do not result in an increased cardiovascular risk.
The Liraglutide Effect and Action in Diabetes Evaluation of Cardiovascular Outcome Results (LEADER) trial was a large, long-term, multi-centre, multi-national, randomized, double-blind, placebo-controlled, trial in adults with T2D at high risk of cardiovascular disease. LEADER was designed as a non-inferiority trial to show that, in addition to regular treatment, Victoza did not increase cardiovascular risk in patients with T2D at high risk of cardiovascular disease, compared to placebo. Based upon the sponsors conclusion that the study achieved this goal, another analysis was conducted to determine if the risk of cardiovascular disease was reduced in patients taking Victoza.
Why was the decision issued?
The LEADER trial demonstrated that in addition to standard of care, Victoza was non-inferior to placebo in the development of major cardiovascular side-effects in adult subjects with T2D at high risk of cardiovascular disease. These results are reassuring, as they show that, when used in patients with T2D at high risk of cardiovascular disease, Victoza does not cause an increased cardiovascular risk.
The sponsor then conducted a further analysis (for superiority) to determine if the risk of cardiovascular disease was reduced in patients taking Victoza. In a subset of patients with a history of cardiovascular disease (i.e., prior heart attack, heart failure, or stroke), Victoza resulted in a 17% decrease in major cardiovascular side-effects and a 26% decrease in cardiovascular deaths compared to placebo. This means that one major cardiovascular side-effect can be prevented for every 44 patients treated with Victoza for three years and one cardiovascular death can be prevented for every 73 patients treated with Victoza for three years.
The LEADER trial was designed as a non-inferiority trial to rule out any extra cardiovascular risk with use of Victoza compared to placebo, in patients at high risk of cardiovascular disease. Although the study was not designed to show a cardiovascular benefit, the Biologics and Genetic Therapies Directorate (BGTD) considers there to be enough evidence to support an expansion to the Victoza indication for a reduction in cardiovascular deaths in adults with T2D, with a history of cardiovascular disease.
The LEADER trial did not show any important new safety risks with the use of Victoza, in patients at high risk of cardiovascular disease.
Use of Victoza in patients with T2D at high risk of cardiovascular disease does not lead to an increased risk of cardiovascular side-effects, resulting in a positive benefit-risk assessment. Further, despite some limitations in study methodology and subgroup analysis, the BGTD considers there to be enough evidence to conclude a favourable benefit-risk profile for Victoza for the reduction of cardiovascular death in adult patients with T2D and a history of cardiovascular disease.
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.