A Treatment Option for Uncontrolled Partial-Onset Seizures

The rationale for treating patients with uncontrolled partial-onset seizures with perampanel based on data from clinical trials, including the FAME study, and important insight on dosing the therapy.

Amit Verma, MD: In any situation where a patient fails their first antiepileptic medication, perampanel [Fycompa] would be an appropriate next choice of medication for a variety of reasons. No. 1, as shown by both the FREEDOM and FAME studies, the efficacy of Fycompa [perampanel], when used early on, is really quite good. In the FAME study, seizure-free rates were close to 50%. I think 47% of patients became seizure-free in that study.

Perampanel has a very long half-life. So if there is a concern of patients having seizures because of missing their medication, this just becomes a very easy choice, under those circumstances.

Based on data published in the New England Journal of Medicine in the early 2000s, the chance of a person becoming seizure-free was only 13% if they failed their first medication and the second medication was added. Based on the results of the FAME study, even though these are obviously different patient populations with different methodologies for studying these patients, when perampanel was added at first monotherapy failure, the chance of becoming seizure-free were really quite high. It was just under 50%—close to 47%. So at least based on the data that we have available, perampanel, when used early, can be quite effective.

Obviously if somebody has failed monotherapy, when deciding which medication we will use first, we ask, “Does it have a long half-life?” We can get up to effective doses in a relatively short period of time. Perampanel, for instance, has a very long half-life—around 105 hours. We typically titrate the dose up every 2 to 3 weeks. Based on the results of the FAME study, the majority of the patients in that study were on 4 mg a day—either 4 or 6 mg, but the majority of them were on 4 mg of the drug. So we can reach effective doses of Fycompa [perampanel] within 2 weeks of initiating treatment.

Looking at the trial design, the investigators added Fycompa [perampanel] at first monotherapy failure. These were patients who were either on or not on enzyme inducers. Fycompa [perampanel] was added and then titrated up. They basically looked at the data and said, “OK, what are the most common doses being used in these patients to achieve seizure freedom?” Or, “What doses achieve a good reduction in seizures?” The vast majority of patients went on 4 mg a day of the drug followed by 6 mg a day, and good efficacy was seen at both doses.

The most common adverse effects that were seen with Fycompa [perampanel] were issues we expected because of using it before. Things like somnolence and dizziness were noted. However, the overall risk of 1 of the things that was seen in both the FREEDOM and the FAME studies was that there were no patients who had homicidal ideation. The risk of psychiatric adverse effects was very low. 

All this information should really give people quite a bit of assurance that this is a safe medication to use at those doses.