Perampanel is a non-competitive AMPA-type glutamate receptor antagonist being developed by Eisai. AMPA receptors are widely present in almost all excitatory neurons.
"Most of the epilepsy drugs we have available are either channel-acting drugs or have been working on the inhibitory side, increasing gamma-aminobutyric acid," said Jacqueline A. French, Director of the Clinical Trials Consortium at New York University’s Epilepsy Center. "This is the first of the antiepileptic drugs that actually blocks the excitatory side—it’s an AMPA antagonist. And my hope is that perhaps by blocking excess excitation, you might actually have the potential to decrease excitatory damage."
Administered once daily, perampanel also has the potential to reduce pill burden.
Three randomised, double-blind, placebo-controlled Phase III studies in a total of 1,480 epilepsy patients showed that perampanel significantly reduced the frequency of partial-onset seizures. All studies involved a 6-week dose titration period, followed by a 13-week maintenance phase.
In study 306, investigators randomised 712 patients to receive perampanel 2mg, 4mg or 8mg daily, or placebo. Intention to treat analysis showed:
- Greater reductions in mean seizure frequency with the 4mg and 8mg doses of perampanel than with placebo: 28.6% (p=0.003) and 33.5% (p<0.001), respectively, versus 13.8%;
- Higher response rates with these doses than with placebo: 28.6% (p=0.009) and 34.9% (p<0.001), respectively, versus 17.6%.
In study 304, 308 patients received perampanel at daily doses of 8mg or 12mg. Consistent with the results of study 306, intention-to-treat analysis showed:
- Greater reductions in mean seizure frequency with perampanel than with placebo: 26.3% and 34.5% at the 8mg and 12mg doses respectively, versus 21.0%;
- Higher response rates with these doses than with placebo: 37.6% and 36.1%, respectively, versus 23.4%.
Study 305 was of identical design to study 304. Full results will be presented at the 29th International Epilepsy Congress in Rome, which takes place from 28 August to 1 September, 2011.
The most frequent treatment-emergent adverse events in studies 304 and 306 were dizziness, headache and somnolence.