Regulatory Decision Summary for BRIVLERA

Epilepsy is a chronic neurological disorder that affects up to about 3% of the population worldwide. The main symptom of epilepsy is the recurrence of unprovoked seizure attacks. Majority of the patients with epilepsy rely on adjunctive treatment (>1 antiepileptic drugs) to control their attacks. Although the ideal goal is to achieve seizure-free status, drastic reduction of frequency of attacks remains the principal objective. Therefore, there is room for improvement in the quality of therapy and new drugs that provide better efficacy with improved adverse event profile.

At this time, there are no post-marketing data for Brivlera (brivaracetam). Based on three pivotal trials, the evidence for Brivlera efficacy is sufficient. Based solely on clinical trial data and compared to a number of other AEDs, including the only other AED member of the racetam family of drugs, Brivlera does appear to have a slightly better safety profile. Thus, based on the totality of safety and efficacy data currently available to Health Canada, the requirements for issuance of a Notice of Compliance (NOC) have been met. There is no doubt that some patients whose seizures are not satisfactorily controlled can benefit from the addition of Brivlera to their current therapeutic regimen.

Safety issues raised during the review of this submission include hematologic, hypersensitivity, psychiatric, as well as dizziness, somnolence, and gait disorders. Pharmacokinetic data support a reduction in the initial and maximum recommended daily doses of Brivlera in patients with varying degrees of hepatic impairment. Pharmacokinetic data also suggest that Brivlera metabolites can accumulate in patients with moderate or severe renal impairment. Although non-clinical data do not show any toxicity due to exposure to accumulating levels of these metabolites, the effects in humans remain uncertain at this time. Proper cautionary statements regarding this issue have been added to the Brivlera Product Monograph. All other safety issues currently known to Health Canada have also been properly labelled and the potential risks associated with the administration of this product can be appropriately managed at this time.

For more information on Health Canadas decision, please view the Summary Basis of Decision.