EMA Accepts MAA Filing of Eisai’s Perampanel for the Treatment of Epilepsy
By Eisai, PRNESunday, June 26, 2011
HATFIELD, England, June 27, 2011 -
Eisai today announced that the European Medicines Agency (EMA)
has accepted for review the Marketing Authorisation Application
(MAA) for perampanel as a treatment for partial-onset seizures in
patients with epilepsy. Perampanel is a first-in-class, highly
selective non-competitive AMPA-type glutamate receptor
antagonist.
Epilepsy is one of the most common neurological conditions in
the world and an estimated 6 million people live with epilepsy in
Europe.[1] The successful treatment of partial-onset
seizures (the most common type of epilepsy) remains a challenge. Up
to 30% of patients with partial-onset seizures do not achieve
seizure freedom despite appropriate therapy with anti-epileptic
drugs.[2]
“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,”
commented, Professor Bernhard Steinhoff, Medical Director and
Executive Chief Physician of the epilepsy clinic for adults, Kork
Epilepsy Centre, Germany. “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.”
The efficacy, safety and tolerability of perampanel has been
demonstrated by three Phase III global, randomized, double-blind,
placebo-controlled, dose-escalation studies in 1,480 epilepsy
patients. 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.
Each of the studies showed consistent results in the efficacy
and tolerability of perampanel in patients with partial-onset
seizures.
Perampanel also has the benefit of once daily dosing, helping to
reduce the potential pill-burden a person with epilepsy may
experience.
“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,” said Lynn D. Kramer, M.D., FAAN,
President, Eisai Neuroscience Product Creation Unit.
”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.”
The development of perampanel is a good example of Eisai’s
human health care corporate mission, the company’s
commitment to innovative solutions in disease prevention, cure and
care for the health and well being of people worldwide. Eisai
is committed to the therapeutic area of epilepsy and addressing the
unmet medical needs of patients with epilepsy and their
families.
Eiasi has also simultaneously submitted a New Drug Application
(NDA) to the U.S. Food and Drug Administration (FDA) for perampanel
for adjunctive treatment of partial-onset seizures associated with
epilepsy.
About Perampanel
Perampanel is a highly selective, non-competitive AMPA
(α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type
glutamate receptor antagonist that has demonstrated anti-seizure
effects in Phase II and III studies. AMPA receptors, widely present
in almost all excitatory neurons, transmit signals stimulated by
the excitatory neurotransmitter glutamate within the brain and are
believed to play a role in central nervous system diseases
characterized by excess neuroexcitatory signalling including
epilepsy, neurodegenerative disorders, movement disorders, pain and
psychiatric disorders.
If approved, perampanel will be the first product in this
class.
About the perampanel Phase III studies
(Study 306, 305 and 304)
The clinical development plan for perampanel consisted of three
global Phase III studies: Studies 306, 305 and 304 in which a total
of 1,480 patients participated. The key goal of Study 306 was to
identify the minimal effective dose and included four treatment
arms (placebo, 2mg, 4mg, and 8mg). Studies 304 and 305 included
three arms (placebo, 8mg, and 12mg) and were to evaluate a more
extended dose range.
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 studies: percentage change in seizure frequency, 50% responder
rate, percentage reduction of complex partial plus secondarily
generalized seizures, and evaluation for dose response.
Study 306[3]
Study 306 showed that perampanel was well-tolerated and
effective in reducing median seizure frequency and increasing
responder rates. Specifically the results showed:
- The results of the full ITT population showed: 2 mg = -13.6%
(p=0.420), 4 mg = -23.3% (p=0.003), 8 mg = -30.8% (p<0.001). A
significant change in median seizure frequency for the ITT
population receiving 4 and 8 mg perampanel/day compared to placebo
was: -28.6% for 4 mg (p=0.003) and -33.5% for 8 mg (p<0.001)
versus -13.8% with placebo. - The results of the full ITT population showed: 2 mg = 20.6%
(p=0.486), 4 mg = 28.5% (p=0.013), 8 mg = 34.9 (p=0.0003). Higher
responder rates compared to placebo for the ITT population: 20.9%
(p=ns), 28.6% (p=0.009), and 34.9% (p<0.001) in the 2, 4, and 8
mg perampanel/day groups, respectively, versus 17.6% with
placebo. - The most frequent treatment-emergent adverse events were
dizziness, headache and somnolence.
Study 305 - Europe, USA,
South Africa, Israel,
Russia, India, Australia
Full results of study 305 will be presented at the
29th International Epilepsy Congress in Rome,
28th August -1st September, 2011.
Study 304[4] -
USA, Canada and South
America
Study 304 showed consistent results in the efficacy and
tolerability of perampanel given as a treatment for patients with
partial-onset seizures. Specifically:
- A full intention-to-treat analysis indicated that the placebo
group, the 8-mg group, and the 12-mg group had a 21.0%, 26.3%, and
34.5% reduced seizure frequency, respectively. - The 50% responder rates in the placebo group, 8-mg group, and
12-mg group were 23.4%, 37.6%, and 36.1%, respectively. - The most common side effects were dizziness, somnolence,
irritability, headache, falls, and ataxia.
About Epilepsy
Epilepsy is one of the most common neurological conditions in
the world, affecting approximately 8 in 1,000 people in
Europe[5]. There is an estimated 6 million people living
with epilepsy in Europe[1] and estimated
50 million people worldwide.[6]
Epilepsy is characterised by abnormal firing of impulses from
nerve cells in the brain causing seizures. Depending on the seizure
type, seizures may be limited to one part of the body, or may be
generalised to involve the whole body.
In partial-onset seizures, these bursts of electrical activity
are initially focused in specific areas of the brain,[7]
but may become generalised;[7] the symptoms
vary according to the affected areas.[8]
Patients may also experience abnormal sensations, altered
behaviour or altered consciousness. Epilepsy is a disorder with
many possible causes. Often the cause of epilepsy is unknown.
However, anything that disturbs the normal pattern of neuron
activity - from illness to brain damage to tumours, can lead to
seizures.[9]
Treatment of partial-onset seizures, the most common type of
epilepsy, presents a constant challenge - Up to 30% of patients
with partial seizures do not achieve remission despite appropriate
therapy with anti-epileptic drugs.[2]
Furthermore, central nervous system related adverse events, such
as lightheadedness (dizziness), somnolence (sleepiness), cognitive
slowing (attention and memory deficits) and aggression, are highly
prevalent with existing anti-epileptic
agents.[10,11,12] Hence, there is a need for
new anti-epileptic agents that offer effective reduction in seizure
frequency combined with a favourable safety profile.
About Eisai Europe in Epilepsy
Eisai is committed to developing and delivering highly
beneficial new treatments to help improve the lives of people with
epilepsy. The development of anti-epileptic drugs (AEDs) is a major
strategic area for Eisai in the European market.
In Europe, Eisai currently has three marketed treatments
including:
- Zonegran® (zonisamide) as adjunctive therapy in
adult patients with partial-onset seizures, with or without
secondary generalization. - Zebinix® (eslicarbazepine acetate) as adjunctive
therapy in adult patients with partial-onset seizures, with or
without secondary generalization. (Zebinix is under license from
BIAL) - Inovelon® (rufinamide) for adjunctive treatment, 4
years and older of seizures associated with Lennox-Gastaut
Syndrome.
About Eisai
Eisai is one of the world’s leading research-based
pharmaceutical companies that has defined its corporate mission as
“giving first thought to patients and their families and to
increasing the benefits health care provides,” which we call
human health care (hhc). Eisai concentrates its research
activities in three key areas
- Neuroscience including: Epilepsy, Alzheimer’s disease,
multiple sclerosis, neuropathic pain and depression. - Oncology including: anticancer therapies; tumour
regression, tumour suppression, antibodies, etc and supportive
cancer therapies; pain relief and nausea. - Vascular/Immunological Reaction including: acute
coronary syndrome, atherothrombotic disease, sepsis, rheumatoid
arthritis, psoriasis and Crohn’s disease.
With operations in the U.S., Asia, Europe and its domestic home
market of Japan, Eisai employs more than 11,000 people
worldwide.
In Europe, Eisai undertakes sales and marketing operations in
over 20 markets, including the United Kingdom, France, Germany,
Italy, Spain, Switzerland, Sweden, Ireland, Austria, Denmark,
Finland, Norway, Portugal, Iceland, Czech Republic, Hungary,
Slovakia, the Netherlands, Belgium and Luxembourg.
For further information please visit our web site
References
1. ILAE/IBE/WHO, Epilepsy in the WHO European Region:
Fostering Epilepsy Care in Europe 2010. Available from;
www.ilae-epilepsy.org/Visitors/Documents/EUROReport160510.pdf
(Accessed June 2011)
2. Kwan P, Brodie MJ Early
identification of refractory epilepsy. New England Journal of
Medicine 2000; 342: 314-9.
3. G. L. Krauss, J. M. Serratosa, V. E. Villanueva, M.
Endziniene, Z. Hong, J. French, H. Yang, D. Squillacote, J. Zhu, A.
Laurenza, American Epilepsy Society Efficacy and safety of
perampanel, an AMPA receptor antagonist, as an adjunctive therapy
in a Phase III study of patients with refractory partial-onset
seizures. Available at URL
www.aesnet.org/go/publications/aes-abstracts/abstract-search/mode/display/st/perampanel/sy/2010/sb/All/id/13437
(Accessed June 2011)
4. Perampanel Reduces
Treatment-Resistant, Partial-Onset Seizures. Neurology Reviews
2011;19(6):1,26-29.
5. Pugliatti M et al. Estimating the
cost of epilepsy in Europe: A review with economic modeling.
Epilepsia 2007: 48(12) 2224 - 2233
6. Epilepsy Society UK:
www.epilepsysociety.org.uk/AboutEpilepsy/Whatisepilepsy/Epilepsy-didyouknow
(Accessed June 2011)
7. Epilepsy Action. Describing Seizure Types. Avaiable at URL
(Accessed June 2011)
8. NHS Choices. Symptoms of Epilepsy. Available at URL
(Accessed June 2011)
9. Epilepsy Research UK. What is Epilepsy? Fact sheet.
Avaiable from URL:
www.epilepsyresearch.org.uk/about_us/leaflets/lflt1.htm
(accessed March 16 2011)
10. Topamax Summary of Product Characteristics. Available
at:
(Accessed June 2011)
11. Carbamazepine Summary of Product Characteristics.
Available at:
www.medicines.org.uk/EMC/medicine/1328/SPC/Tegretol+Chewtabs+100mg%2c+200mg%2c+Tegretol+Tablets+100mg%2c+200mg%2c+400mg/
(Accessed June 2011)
12. Oxcarbazepine Summary of Product Characteristics.
Available at:
www.medicines.org.uk/emc/medicine/2673/SPC/#INDICATIONS
(Accessed June 2011)
Media Enquiries, Eisai Europe Ltd, Cressida Robson, +44-7908-314-155, Cressida_Robson at eisai.net Tonic Life Communications, Benjamyn Tan / Helen Swift, +44(0)7747111217 / +44(0)207-798-9900, benjamyn.tan at toniclc.com, helen.swift at toniclc.com
Tags: Eisai, England, Hatfield, June 27, United Kingdom
