Regulatory Decision Summary for Aptiom

Currently, the majority of patients with epilepsy rely on adjunctive treatment (more than one AED) to control their seizures. Most AEDs that are marketed in Canada are indicated for use as adjunctive therapy. Polytherapy has been reported to be the standard of care in epilepsy and has long been given as initial treatment. Monotherapy is preferred over polytherapy since patients are treated with one AED instead of a few products each of which can cause a set of adverse events and may also interact with one another. Thus, it would be ideal to initially treat patients that are newly or recently diagnosed with epilepsy with a single AED. More recent data indicate that a large number of patients given initial monotherapy remained seizure-free for up to one year.

This submission consisted of Study 311, an active-controlled (carbamazepine controlled release; CBZ-CR), non-inferiority trial which tested the safety and efficacy of ESL doses 800, 1,200, and 1,600 QD in patients with newly or recently diagnosed partial-onset seizures. Data from this study showed that Aptiom (800 to 1600 mg/day) was non-inferior to CBZ-CR (400 to 1,200 mg/day) in terms of efficacy. Safety data in this study were similar to the previously known profile of Aptiom (when used as adjunctive therapy). This study also showed that up to approximately one year, efficacy was maintained and safety profile of Aptiom remained unchanged.

The majority of patients were satisfactorily controlled at the lowest dose (800 mg / day). However, the dosing recommendations for monotherapy have a higher maximum daily dose (1,600 mg / day) compared to when Aptiom is used as adjunctive therapy (1,200 mg / day). Despite the difference in the maximum dose, the safety profiles of the two different treatment regimens are similar.

All safety issues currently known to Health Canada have been labeled properly. Therefore, the Benefit-Harm-Uncertainty of Aptiom used as monotherapy in adult patients with newly or recently diagnosed partial-onset seizures is favourable.