Eisai, a Japanese pharmaceutical company, has disclosed that its Marketing Authorization Application (MAA) for a new first-in-class epilepsy drug, perampanel, had been accepted for review by the European Medicines Agency (EMA). The medication is aimed to treat the most common type of epilepsy (partial-onset seizures) and is a highly selective non-competitive AMPA-type glutamate receptor antagonist.
Epilepsy is a very common neurological condition across the globe with Europe alone believed to have 6 million people who suffer from the condition. Even in today’s modern world with drugs being available for most disease forms, it is a challenge to successfully treat episodes of partial onset seizures. Although anti-epileptic drugs are prescribed to all patients with partial onset seizures, up to 30% never attain complete seizure freedom.
Professor Bernhard Steinhoff, Medical Director and Executive Chief Physician of the epilepsy clinic for adults, Kork Epilepsy Centre, Germany said:
“The acceptance of this application by the EMA is a positive step in the process towards bringing this important therapy to epilepsy patients with uncontrolled partial-onset seizures. “Uncontrolled seizures have a severe impact on patient quality of life and everyday function, so we look forward to the possibility of being able to offer epilepsy patients a new treatment option in the near future.”
Three large Phase III, randomized, double-blind, placebo-controlled, dose-escalation studies in which a total of 1,480 epilepsy patients were enrolled globally have clearly demonstrated consistent safety, efficacy and tolerability results for perampanel in effective treatment of partial-onset seizures.
The primary and secondary endpoints were the same in all the studies: 50% responder rate, standard median percent seizure reduction, percentage reduction of complex partial plus secondarily generalized seizures, and evaluation for dose response.
In addition to being a potential new treatment for epilepsy, perampanel has extra benefits. Made possible by once daily dosing of perampanel, one such benefit is the reduction of pill-burden that patients with epilepsy routinely encounter.
Dr. L. D. Kramer, M.D., FAAN, President, Eisai Neuroscience Product Creation Unit said:
“As a research-based pharmaceutical company with a particular focus on epilepsy, we are committed to bringing innovative new epilepsy therapies to market that offer patients the opportunity for improved seizure control,” “Perampanel is an exciting new product that has the potential to address the strong unmet need in epilepsy patients and fits entirely within Eisai’s human health care mission.”
Eisai has also submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the same drug for adjunctive treatment of partial-onset seizures associated with epilepsy.
Perampanel is a highly selective, non-competitive AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptor antagonist. It has exhibited anti-seizure effects in Phase II and III studies.
Nerve signals stimulated by the excitatory neurotransmitter glutamate within the brain are transmitted by AMPA receptors which are extensively present in excitatory neurons. These receptors are believed to play a significant role in all neurological illnesses characterized by excess neuroexcitatory signaling, such as epilepsy.
If approved by EMA or FDA, perampanel will be the first product in this class.
Three global phase III studies (Study 306, 305 and 304) were conducted as a part of the clinical development program for perampanel in which a total of 1,480 patients across multiple study centers were enrolled.
Identification of the minimal effective dose of perampanel was the main objective of Study 306 and was designed to have four treatment arms (placebo, 2mg, 4mg, and 8mg). To evaluate a more extended dose range, Studies 304 and 305 were conducted. They were designed to have three treatment arms (placebo, 8mg, and 12mg).
The studies were similar in design: global, randomized, double-blind, placebo-controlled, dose-escalation, parallel-group studies. The primary and secondary endpoints were the same in all the trials: percentage change in seizure frequency, 50% responder rate, percentage reduction of complex partial plus secondarily generalized seizures, and evaluation for dose response.
Epilepsy, a common neurological disorder affects an estimated 50 million people across the globe with approximately 6 million in Europe alone. Statistics indicate that 0.8% of individuals in Europe (8 in every 1,000) are affected by this illness.
Epilepsy causes a person to have seizures which result from unusual firing of impulses from neurons in the brain. Seizures may involve the whole body or only a part of it. In partial-onset seizures, this abnormal brain activity may initially only occur in specific areas which can gradually become generalized.
In addition to experiencing seizures, patients can also complain of abnormal sensations, altered behavior or altered consciousness.
Epilepsy is an illness with multiple possible causes, but in most cases the exact cause is not known.
Anything that has a potential to disturb the normal pattern of brain cell activity – from illness to brain damage to abnormal mass, can lead to seizures.
It is always difficult to treat partial-onset seizures; the most common type of epilepsy. Although anti-epileptic drugs are prescribed to all patients with partial onset seizures, up to 30% never attain complete seizure freedom.
In addition, almost all existing anti-epileptic agents in the marketplace are known for side effects, such as lightheadedness (dizziness), somnolence (sleepiness), cognitive slowing (attention and memory deficits) and aggression.
Written by Barry Windsor