Regulatory Decision Summary for Vyvanse

The positive Benefit-Harm-Uncertainty (BHU) decision for Vyvanse in binge-eating disorder (BED) was based on a combination of three positive efficacy and safety studies, as well as considerable knowledge of the drug effects. Vyvanse has been approved for use in Canada for the treatment of attention-deficit hyperactivity disorder (ADHD) since 2009, and the active agent (d-amphetamine) has been on the market for decades, and often used off label as a performance enhancer, for anti-fatigue, and weight loss. The approval of the BED indication for Vyvanse by the United States Food and Drug Administration (FDA) in January 2015 is the first approval internationally of a drug for BED.

Efficacy of Vyvanse was demonstrated in two identical 12-week placebo-controlled studies in adults with moderate to severe BED (at least 3 binge-eating days per week), with flexible dosing of 50 or 70 mg/day. The primary efficacy outcome for the two studies was defined as the change from baseline in the number of mean binge days per week at Week 11/12. The results showed a robust clinically and statistically significant reduction of drug over placebo (mean of 1.7 and 1.4 fewer binge-eating days per week), as well in a key secondary endpoint of "proportion of patients with at least 4-week cessation in binge-eating at the end of the study" (~40% vs. ~15%, pooled from the two studies). Longer-term efficacy was assessed via observed relapse in a 9 month Randomized-Withdrawal study (12 week open-label optimization to 50 or 70 mg/day, with responders blindly randomized to placebo or to continue drug, for up to 6 months), in adults with moderate to severe BED. The Kaplan-Meier estimates of the risk of relapse after 180 days of treatment showed a significant difference compared to placebo: 4% in the Vyvanse group and 36% in the placebo group. The findings in the 12 week and 9 month studies support a recommended dose range of 50-70 mg day.

No new safety issues for Vyvanse were identified in this review. The primary labelled harms associated with Vyvanse and the class of amphetamines include: elevations in heart rate and blood pressure; sudden cardiac death/stroke; peripheral vasculopathy (for example, Reynauds Syndrome); drug abuse, physical dependence; emergence of new psychotic/manic symptoms; suicidality; weight loss /suppression of growth in children. There was no signal in the BED population to suggest enhanced warnings were needed (other than for cardiovascular (CV) risk, as below). Notable adverse effects seen in the BED trials, and also ADHD trials, include insomnia, irritability, nausea, feeling jittery/restless/racing thoughts.

Uncertainties /Gap: The main issue with this submission concerns potential cardiovascular (CV) risks when a stimulant drug such as Vyvanse is used in the BED population, as most patients seeking treatment for this condition are obese. Patients with a higher CV risks were excluded from the BED trials (moderate or severe hypertension, diabetes, and various CV conditions/disease), and the sponsor has no plans to conduct a post-market CV outcomes trial (COT). In consultation with the expert who reviews COT trials on possible risk mitigation strategies, it was determined that the current Contraindications and Warnings and Precautions in the Vyvanse Product Monograph (PM) were likely sufficient to exclude the patients that are at higher risk of CV adverse events. In addition, more information was included in the Vyvanse PM, to disclose the limitations of the BED clinical data to evaluate potential increased CV risks in the BED population and to advise prescribers to consider those potential risks. This information was also added to the Patient Information section (Part III).