Regulatory Decision Summary for Vyvgart

The purpose of this submission is to seek market authorization for Vyvgart (efgartigimod injection) for the treatment of adult patients with generalized myasthenia gravis (gMG).

The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

The efficacy of Vyvgart for the treatment of adult patients with gMG who are anti acetylcholine receptor antibody (AChR-Ab) seropositive was demonstrated in a 26-week double-blind, placebo-controlled trial that enrolled 167 individuals with gMG who were on stable background therapy. Subjects received a 4-week treatment cycle of once weekly infusions of either Vyvgart or placebo with a 24-week follow-up period. Efficacy was assessed 8 weeks after the initiation of treatment, i.e., at the end of the treatment cycle.

The primary efficacy endpoint was the percentage of Myasthenia Gravis-Specific Activities of Daily Living (MG-ADL) responders during the first treatment cycle in the AChR-Ab seropositive population. The key secondary efficacy endpoint was the percentage of Quantitative Myasthenia Gravis (QMG) responders during cycle 1 in the AChR-Ab seropositive population.

Vyvgart was superior to placebo on the primary endpoint. Efficacy was further supported by the results for the key secondary endpoint showing a higher percentage of QMG responders in the Vyvgart group compared to the placebo control group. Results were clinically meaningful and statistically significant.

The clinical safety database included 162 patients with gMG who received at least 1 dose of Vyvgart. Common adverse reactions associated with Vyvgart treatment included upper respiratory tract infection, urinary tract infection, bronchitis, myalgia and procedural headache. The majority of adverse reactions were of mild or moderate intensity and non-serious. The proportion of subjects who discontinued treatment due to safety concerns was low. Adverse reactions related to infection were the most commonly reported adverse events in the pivotal study, consistent with Vyvgart’s mechanism of action. The risk of infections, including the occurrence of serious infections has been appropriately labelled in the Product Monograph. Other risks associated with Vygart treatment that have been labelled include the potential for hypersensitivity and infusion-related reactions. The safety database for Vyvgart is considered sufficient to support authorization in the intended population and at the intended dosing regimen; overall, the safety experience with Vyvgart supports an acceptable risk profile. However, owing to the rarity of the disease, uncertainties in the safety profile remain. These uncertainties have been adequately addressed through a combination of labelling and/or through routine and enhanced pharmacovigilance activities in the post-market setting.

Overall, the benefits of Vyvgart outweigh its risks in adult patients with gMG who are AChR-Ab seropositive. The benefit/risk profile of Vyvgart is considered favourable in the target patient population.

For further details about Vyvgart, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.