Regulatory Decision Summary for FYCOMPA

The pivotal trial (study 332) was a Phase III randomized, double-blind, placebo-controlled, adjunctive therapy, 17-week trial including 164 patients. The Randomization Phase consisted of three periods: Titration (4 weeks), Maintenance (13 weeks) and follow-up for those not continuing into the open-label extension (OLE). During the 4-week Titration Period, patients initially received 2 mg of perampanel per day or matching placebo and were up-titrated weekly in 2 mg increments to a target dose of 8 mg per day or the highest tolerated dose. At the completion of the Titration Period, subjects entered the 13-week Maintenance Period on the last dose level achieved at the end of the Titration Period and continued taking this dose once daily for the duration of the Maintenance Period. The outcome of the trial showed strong clinical and statistical significance, through several different analyses (including % reduction in frequency of PGTC seizures; 50% responder rate; seizure-free rate).

The option of increasing the dose beyond 8 mg, up to 12 mg, was provided in the OLE, and 19 of 140 patients did so; there were no safety signals from these open-label data. The totality of data from both the PGTC and the Partial Onset Seizure (POS) populations, in combination with clinical practice, supports identical dosing instructions for the PGTC seizure population as for the POS population.

While the number of patients in the trial was small, it was in line with other anti-epileptic treatments approved for the same indication by the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA). As there was already a sizable POS patient database, and the type of seizure is not expected to impact the overall efficacy or safety profile of the treatment, the smaller number of patients in the PGTC trial is acceptable.

Both EMA and FDA included adolescents in the indication, whereas they were not included in Canada. This is consistent with the previously approved POS indication where Health Canada had excluded adolescents at the time of the approval of the POS indication due to a lack of sufficient data in that population. The sponsor did not request inclusion of the adolescent population for the current PGTC indication.

The adverse event profile from the PGTC study was similar to that seen with the POS studies; this is not unexpected for these populations. Health Canada concluded that no additional warning language was required due to the PGTC data.

Overall, the Benefit-Harm-Uncertainty profile of the PGTC seizure indication is considered positive.