Using Fycompa (perampanel) — an approved anti-seizure treatment for certain types of epilepsy — as an add-on therapy significantly reduced the frequency of seizures in adults with Lennox-Gastaut syndrome (LGS), a recent study shows.
Based on these data, researchers suggested that Fycompa be considered for LGS patients with persistent and disabling seizures. But they recommended that behavioral side effects or seizure aggravation be closely monitored.
The study, “Open-label, uncontrolled retrospective study of perampanel in adults with Lennox-Gastaut syndrome,” was published in Seizure: European Journal of Epilepsy.
LGS is a form of epilepsy characterized by multiple types of seizures, cognitive difficulties, extensive changes in the brain’s electric activity (both awake and asleep), and resistance to many types of anti-seizure medications.
To date, no single therapy has been effective in treating seizures in all LGS patients, so the use of add-on therapies is common.
Fycompa, developed and marketed by Eisai, is an oral anti-seizure therapy approved in more than 55 countries.
While its underlying mechanisms are not well understood, Fycompa is thought to work by blocking AMPA receptors. These are specific proteins involved in the transmission of excitatory signals (or signals between nerve cells in the brain) that are implicated in epilepsy. Fycompa is the first and only anti-seizure medication to date targeting AMPA receptors.
In the U.S., Fycompa is approved, alone or in combination, to treat focal-onset seizures in patients with epilepsy ages 4 and older, and with other medications for the treatment of primary generalized tonic-clonic seizures in people with epilepsy ages 12 and older.
Preliminary reports of Fycompa’s off-label use in people with LGS have suggested that the therapy, as an add-on treatment, may help reduce seizure frequency in these patients.
A team of French researchers evaluated the safety and therapeutic effects of add-on Fycompa therapy in LGS adult patients with persistent, severe, and disabling seizures. All were being followed at two clinics in that country.
The team retrospectively analyzed the clinical data from 71 adults (43 men and 28 women) diagnosed with either LGS (62 patients) or with “LGS-like” epilepsy (nine patients). Their ages ranged from 20 to 71, with a mean age of 40.1.
Patients and caregivers were seen at three-month intervals, and Fycompa was given at gradually escalating doses (with 2 mg increments) up to 6 mg per day, with possible dose adjustments after that.
Fycompa’s effectiveness was assessed by comparing the seizure frequency of the previous three months between the initial visit (before Fycompa initiation) and the latest follow-up or the moment of treatment discontinuation. A therapeutic effect was considered when seizure frequency was reduced by at least 50%.
Fycompa’s effectiveness was assessed by comparing a person’s three-month seizure frequency prior to this add-on treatment’s use to the frequency either at their latest clinic visit or at the moment they stopped treatment. A therapeutic effect was considered when seizure frequency fell by at least 50%.
Patients were receiving a median of three anti-seizure medications at the time of Fycompa’s initiation. Fycompa was administered for a median of 538 days (nearly 1.5 years), and 22 people (31%) reduced the number of anti-seizure treatments they were using during that time.
Data showed that 46 patients (64.8%) had at least a 50% reduction in seizure frequency, including 25 (35.2%) who showed a reduction of at least 75%. Among these, 12 (16.9%) had a 90% or greater decrease in seizure frequency.
Among the 25 patients (35.2%) who did not respond to Fycompa, five had a less than 50% improvement in seizure frequency, 14 showed no improvement, and six had an increase in seizure frequency (seizure aggravation).
Half of all patients reported at least one side effect, mostly experienced at a daily 6 mg dose. A total of 23 patients (32%) had significant negative changes in behavior, including irritability (8.5%), aggressiveness (7%), and agitation (2.8%), and four reported positive behavioral and psychological effects, including a feeling of wellness, calm, and better interactions with others.
Side effects led 17 patients (24%) to stop treatment, including six who did so because of seizure aggravation, and 10 others (including three who were initial responders) who found it ineffective.
Researchers noted that the frequency of Fycompa-associated side effects in these patients was higher than that reported in studies of resistant focal epilepsy, or focal seizures that do not respond to medication. Nevertheless, the team emphasized that Fycompa seemed to be at least as effective as other currently used treatments in LGS patients.
Fycompa “should be tried in LGS patients who are not satisfactorily controlled. Its use may be limited in some patients due to behavioral side-effects occurring, particularly at doses [of at least] 6 mg/d,” researchers said.
The team noted that future studies are required to confirm Fycompa’s therapeutic benefits and potential associations with several factors, including age, treatment duration, and other medications.
One author of this study is a member of Eisai’s advisory board.