Overview

The content of this evidence summary was up-to-date in December 2012. See summaries of product characteristics (SPCs), British national formulary (BNF), BNF for children (BNFc) or the MHRA or NICE websites for up-to-date information.

Key points from the evidence

Perampanel is a first-in-class selective, non-competitive antagonist of the AMPA glutamate receptor. It is licensed for the adjunctive treatment of partial-onset seizures with or without secondarily generalised seizures in people aged 12 years and older with epilepsy.

The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care (NICE clinical guideline 137) recommends carbamazepine, clobazam, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, sodium valproate or topiramate as adjunctive treatment if monotherapy is ineffective or not tolerated. If adjunctive treatment is ineffective or not tolerated, the guideline recommends that advice should be sought from a tertiary epilepsy specialist. Anti-epileptic drugs that may be considered by the specialist at this point in the care pathway are eslicarbazepine acetate, lacosamide, phenobarbital, phenytoin, pregabalin, tiagabine, vigabatrin, zonisamide, and retigabine (as recommended in Retigabine for the adjunctive treatment of adults with partial onset seizures in epilepsy with and without secondary generalisation [NICE technology appraisal guidance 232]).

In clinical studies, adjunctive treatment with perampanel 4 to 12 mg once daily has been shown to reduce seizure frequency in people aged 12 years and older with partial-onset seizures and a baseline median seizure frequency ranging from 9.3 to 14.3 per 28 days. In 2 phase III studies (n=386 and n=706, follow-up 19 weeks), seizure frequency decreased by at least half in 33.3% and 34.9% of patients taking perampanel 8 mg daily, compared with 14.7% and 17.9% of patients taking placebo. A third study (n=388, follow-up 19 weeks) did not show a statistically significant reduction in seizure frequency. However, the European Medicines Agency concluded that this was due to regional differences in placebo response and concomitant use of enzyme-inducing anti-epileptic drugs in patients recruited to the trials, and does not suggest a lack of efficacy in European populations (see Clinical effectiveness).

A number of adverse events (78.2% of 1186 patients in an open label extension study) were associated with perampanel treatment, and many appeared to be dose related. Central nervous system adverse events such as dizziness, somnolence, headache and fatigue were seen most commonly. The long-term adverse effects of perampanel are unknown.

Local decision makers will need to consider the place of perampanel alongside the use of other available adjunctive treatments for partial-onset seizures. It is unclear how perampanel compares with other drugs used at this stage in the care pathway. Specialists have suggested that perampanel is an option for the adjunctive treatment of partial-onset seizures with or without secondary generalisation in people aged 12 years and older with epilepsy, when standard adjunctive treatment (with carbamazepine, clobazam, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, sodium valproate or topiramate) has not provided an adequate response, or has not been tolerated.

Key evidence

French JA, Krauss GL, Biton V et al. (2012) Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology 79: 589–96

French JA, Krauss GL, Steinhoff BJ et al. (2012) Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: Results of randomized global phase III study 305. Epilepsia doi: 10.1111/j.1528-1167.2012.03638.x

Krauss GL, Serratosa JM, Villanueva V et al. (2012) Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology 78: 1408–15

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.