Authors: Alice Weatherston
Data presented at the American Epilepsy Society Annual Meeting (4–8 December 2015, Philadelphia, PA) earlier this week highlighted the range of data now supporting the use of perampanel (Fycompa®) for multiple types of epileptic seizures. Epilepsy expert Eugen Trinka from Paracelsus Medical University, Salzburg, Austria has been involved with some of these trials and has experience of the use of perampanel in the clinic. We discussed his experiences of the drug and why he thinks it has had such a big impact at this year’s meeting.
Perampanel data from the meeting primarily focused on the efficacy of the drug in the reduction of primary and secondary generalized tonic-clonic seizures. A post-hoc pooled analysis of Phase III data indicated a median 65.5% reduction in primary and secondary generalized seizure frequency over 28 days versus placebo. In addition to this, 26.9% of participants achieved seizure-free status with perampanel compared to 12.6% of people with placebo, with the drug also being well-tolerated.
One advantage of perampanel is its broad efficacy, acting against focal and partial seizures as well as primary generalized seizures explained Eugen Trinka: “The key issue is that most drugs don’t work against primary generalized [seizures], they only work against focal generalized tonic-clonic seizures, so that’s an advantage.”
In addition to this, the novel mechanism of the drug has attracted attention, acting on the AMPA receptor mediated by the major excitatory neurotransmitter, glutamate. “Epilepsy seizures are effectively an imbalance between excitation and inhibition and while many drugs try to increase inhibition, perampanel is the first drug that decreases excitation. One of the advantages of this is that when you decrease excitation you don’t inhibit any other functions, which is the case when you give strong inhibiting drugs like GABAergic drugs which can then result in sedation and other side effects,” explained Trinka. The targeting of glutamate may also be advantageous for individuals for which seizures have developed following acute events such as stroke or brain trauma, as these events often involve glutamergic mechanisms. “To have a drug acting against glutamate or having a reduction in excitation is very interesting.”
As with all clinical trials, testing for safety was key, and the drug was widely well-tolerated in study participants. Despite some minor community concerns regarding adverse behavioral or psychological side-effects associated with its use, Trinka believes from his own experience that this is easily controlled: “If there is any psychiatric abnormality or a psychiatric disorder you should use perampanel with caution. This can be assessed clinically before prescription and doctors should make a careful risk-benefit analysis before prescribing it to these patients. Otherwise it’s very well-tolerated in my opinion,” he commented.
The overall importance of the drug for epilepsy treatment is clear, explained Trinka: “currently 30–40% of patients are not controlled without adverse effects, so it’s not satisfactory what we have at the moment. We desperately need drugs, especially for those that are affected by the most dangerous seizure type, which is the generalized tonic-clonic seizure.”
He now believes that the next step is to approve perampanel for use as a monotherapy as well as to investigate the disease-modifying properties of the drug. “I think that antiepileptogenesis trials are one of the most exciting areas of epileptology at the moment. In many cases epilepsy is a progressive disorder, so in order to prevent this degeneration it would be good to have drugs that can modify the disease. Perampanel could be one of those, but it must be tested.”
Additional source: Eisai press release