First-in-class Fycompa® (perampanel) Pooled Pivotal Phase III Data Published in Epilepsia

 First-in-class Fycompa® (perampanel) Pooled Pivotal Phase III Data Published
                                 in Epilepsia

  PR Newswire

  HATFIELD, England, May 13, 2013

HATFIELD, England, May 13, 2013 /PRNewswire/ --

   Perampanel is effective and well tolerated for the treatment of partial
seizures when co-administered with the most commonly prescribed anti-epileptic
                                    drugs

Results from a pooled analysis of three large Fycompa (perampanel) trials are
published today in leading clinical and research epilepsy publication,
Epilepsia. ^[1] These new data confirm the efficacy of perampanel as an
adjunctive treatment for hard-to-treat partial seizures and also provides
further reassurance that perampanel is well tolerated.

The publication groups together the three pivotal clinical studies for
perampanel, Study 304, Study 306 and Study 307. The pooled analysis of these
data from nearly 1,500 patients shows that perampanel reduced partial epilepsy
seizure frequency and improved responder rates compared to placebo. ^[ ^1 ^]
At randomised doses of 4-12 mg, perampanel conferred significant improvements
in reducing seizure frequency and 50% responder rates for all partial seizures
and complex partial (CP) seizures with secondary generalisation (SG seizures),
compared with placebo. The analysis also showed that adjunctive perampanel was
efficacious irrespective of the co-administered anti-epileptic drug (AED). ^[
^1 ^]

Perampanel is the only licensed anti-epileptic drug in Europe that selectively
targets AMPA receptors, which are thought to play a central role in seizure
generation and spread. ^[ ^2] This first-in-class treatment selectively
targets the transmission of seizures by blocking the effects of glutamate,
which can trigger and maintain seizures. In addition, perampanel has the added
benefit of convenient, once-daily dosing taken at bedtime. ^[3] Discovered and
developed by Eisai in Europe and Japan, perampanel is the only 3 ^rd
generation epilepsy treatment approved for adolescents.

Perampanel is licensed as an adjunctive treatment for people aged 12 years and
older with partial-onset seizures, with or without secondarily generalised
seizures. ^[ ^3 ^] It was approved by the European Commission in July 2012 and
the US FDA in October 2012. In Europe, it is currently available in the UK,
Denmark, Germany, Sweden, Norway and Austria. Swissmedic, the Swiss Agency for
Therapeutic Products, approved perampanel for use on 17 December 2012.

"These new data are consistent with the results seen in the individual trials
and confirm the clinical value of perampanel in the treatment of partial
seizures," noted Professor Bernhard Steinhoff from the Epilepsiezentrum Kork,
Kehl-Kork, Germany. "Up to 40% of patients with epilepsy are, or become,
refractory to treatment, potentially resulting in impaired quality of life and
an increased risk of injury or unexpected sudden death. There is a real need
for effective new AEDs with novel modes of action that can be given with the
most commonly prescribed AEDs. Perampanel is therefore a very welcome new
adjunctive therapy."

Patients with partial seizures despite receiving 1-3 AEDs, were randomised to
once-daily placebo, perampanel 8 or 12 mg (studies 304 ^[ ^4] , 305 ^[ ^5] ),
or placebo, perampanel 2, 4, or 8 mg (study 306 ^[ ^6] ). Studies included a
6-week baseline period and double-blind treatment phase (6-week titration;
13-week maintenance). Primary endpoints were median change in partial seizure
frequency (baseline vs. double-blind phase) and percentage of patients
achieving ≥50% reduction in seizure frequency (baseline vs. maintenance). In
the pooled analysis, these endpoints, as well as secondary, exploratory, and
safety endpoints, were assessed.

The results of the pooled analysis showed that median reductions in partial
seizure frequency were greater with perampanel 4 mg (-23·3%), 8 mg (-28·8%),
and 12 mg (-27·2%) than placebo (-12·8%; p<0·01, each dose vs. placebo). Fifty
percent responder rates were greater with perampanel 4 mg (28·5%), 8 mg
(35·3%), and 12mg (35·0%) than placebo (19·3%; p<0·05, each dose vs.
placebo). Median reductions in complex partial seizure frequency were greater
with perampanel 4 mg (-31·2%), 8 mg (-35·6%), and 12 mg (-28·6%) than placebo
(-13·9%). Perampanel was generally well tolerated with most adverse events
being mild or moderate.

The development of perampanel underscores Eisai's human health care 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 and their families. Eisai is proud to currently market more
epilepsy products in Europe, the Middle East and Africa (EMEA) than any other
company.

Notes to Editors

About Perampanel

Perampanel is licensed in Europe Union and Switzerland as an adjunctive
treatment for people aged 12 years and older with partial-onset seizures, with
or without secondarily generalised seizures. ^[ ^3 ^]

Perampanel is a highly selective, non-competitive AMPA
(alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate
receptor antagonist that has demonstrated seizure reduction 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 characterised by excess neuroexcitatory signalling including
epilepsy, neurodegenerative disorders, movement disorders, pain and
psychiatric disorders. ^[ ^3 ^]

Further information for healthcare professionals can be found at
http://www.Eisai.co.uk

About the Perampanel pooled data (Study 306, 305 and 304)

The pooled Phase III data analysed the efficacy of once-daily perampanel in
reducing partial-onset seizures, the most common form of epilepsy, and its
effectiveness and flexibility of use as add-on therapy. Efficacy end points
for studies 304, 305, and 306 were pooled according to randomised treatment:
placebo, perampanel 2, 4, 8 or 12mg. The full ITT (intention-to-treat)
analysis set included 1,478 patients from studies 304 (n=387), 306 (n=386) and
306 (n=705).

Median reductions in partial seizure frequency were greater with perampanel 4
mg (-23·3%), 8 mg (-28·8%), and 12 mg (-27·2%) than placebo (-12·8%; p<0·01,
each dose vs placebo). Median (95% CI) differences from placebo in changes in
partial seizure frequency were -12·2% (-20·1 to -4·6), -17·9% (-24·1 to
-11·8), and -15·8% (-23·0 to -8·7) for perampanel 4, 8, and 12 mg,
respectively.

Fifty percent responder rates were greater with perampanel 4 mg (28·5%), 8 mg
(35·3%), and 12mg (35·0%) than placebo (19·3%; p<0·05, each dose vs placebo).
Median reductions in complex partial seizure frequency were greater with
perampanel 4 mg (-31·2%), 8 mg (-35·6%), and 12 mg (-28·6%) than placebo
(-13·9%).

Results from two separate analyses of pooled data from the perampanel pivotal
Phase III clinical trial programme endorse the efficacy and safety of the new
AED at clinically relevant doses. ^[7] In addition, the results show that
perampanel decreased the frequency of both complex partial seizures and
secondarily generalised seizures. ^[8] In a third analysis of the pooled trial
data, patients with uncontrolled partial-onset seizures taking any of the five
most commonly-used AEDs with perampanel as an add-on therapy experienced a
reduction in their seizure frequency. Patients generally received additional
benefit from increased doses of perampanel. ^[9]

Perampanel was generally well tolerated; most adverse events were
mild/moderate.

The clinical development plan for perampanel consisted of three global Phase
III studies (studies 306, 305 and 304). The key goal of Study 306 ^[6 ^] was
to identify the minimal effective dose and included four treatment arms
(placebo, 2mg, 4mg, and 8mg). Study 304 ^[4 ^] and Study 305 ^[5 ^] included
three arms (placebo, 8mg, and 12mg) and were to evaluate a more extended dose
range. The studies were similar in design: global, randomised, 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 generalised seizures, and evaluation for dose response. The
primary endpoint for the EMA is 50% responder rate and for the FDA is median
percent change in seizure frequency.

About Epilepsy

Epilepsy is one of the most common neurological conditions in the world,
affecting approximately eight in 1,000 people in Europe, and an estimated 50
million people with the condition worldwide. ^[10] ^, ^[11] Epilepsy is a
chronic disorder of the brain that affects people of all ages. It is
characterised by abnormal discharges of neuronal activity causing seizures.
Seizures can vary in severity, from brief lapses of attention or jerking of
muscles, to severe and prolonged convulsions. Depending on the seizure type,
seizures may be limited to one part of the body, or may involve the whole
body. Seizures can also vary in frequency from less than one per year, to
several per day. Epilepsy has many possible causes but often the cause is
unknown.

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 AEDs is a major strategic area for Eisai in Europe, the Middle East and
Africa (EMEA).

In the EMEA region, Eisai currently has four marketed treatments including:

  *Zonegran ^® (zonisamide) as monotherapy and adjunctive therapy in adult
    patients with partial-onset seizures, with or without secondary
    generalisation. (Zonegran is under license from the originator Dainippon
    Sumitomo Pharma). In Switzerland, Zonegran is only approved as adjunctive
    therapy.
  *Zebinix ^® (eslicarbazepine acetate) as adjunctive therapy in adult
    patients with partial-onset seizures, with or without secondary
    generalisation. (Zebinix is under license from BIAL). Zebinix is not
    approved by Swissmedic.
  *Inovelon ^® (rufinamide) for the adjunctive treatment of seizures
    associated with Lennox-Gastaut Syndrome in patients >4 years
  *Fycompa ^® (perampanel) for use as an adjunctive treatment for partial
    onset seizures, with or without secondarily generalised seizures, in
    patients with epilepsy aged 12 years and older

About Eisai

Eisai is one of the world's leading research and development (R&D) based
pharmaceutical companies.

Eisai concentrates its R&D activities in three key areas:

  *Neuroscience, including: Alzheimer's disease, epilepsy, pain and weight
    loss
  *Oncology including: anticancer therapies; tumour regression, tumour
    suppression, antibodies, etc
  *Vascular/Immunological reaction including: thrombocytopenia, rheumatoid
    arthritis, psoriasis, inflammatory bowel disease

With operations in the U.S., Asia, Europe and its domestic home market of
Japan, Eisai employs more than 10,000 people worldwide. From its Knowledge
Centre in Hatfield, UK, Eisai has recently expanded its business operations to
include Europe, the Middle East and Africa (EMEA). Eisai EMEA has sales and
marketing operations in over 20 markets, including the United Kingdom, France,
Germany, Italy, Spain, Switzerland, Sweden, Ireland, Austria, Denmark,
Finland, Norway, Portugal, Czech Republic, Slovakia, the Netherlands, Belgium
and the Middle East.

For further information please visit our web site http://www.eisai.co.uk

References

1. Steinhoff B et al. Epilepsia 2013; Efficacy and safety of adjunctive
perampanel for the treatment of refractory partial seizures: a pooled analysis
of three Phase III studies

2. Rogawski MA. Epilepsy Currents 2011;11:56-63

3. Fycompa Summary of Product Characteristics. 2012

4. French JA. Neurology 2012;79:589-596

5. French J, et al. 2011, IEC Rome. Abstract #122/ Ref 020

6. Krauss GM. Serratosa JM, Villanueva V et al. Neurology 2012: Available at:
http://www.neurology.org/

7. Ben-Menachem E,Krauss GL, Noachtar S et al. Abstract presented at ECE 2012

8. Steinhoff BJ, Gauffin H, McKee P et al. Abstract presented at ECE 2012

9. Trinka E, Straub H, Squillacote D et al. Abstract presented at ECE 2012

10. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe
http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf [Accessed
August 2012]

11. Pugliatti M, et al. Epilepsia Estimating the cost of epilepsy in Europe: a
review with economic modelling. 2007: 48(12);2224-2233

Date of preparation: May 2013 Job code: Perampanel-UK2121



Contact: Media Enquiries: Eisai Europe Ltd., Charlotte Andrews / Cressida
Robson, +44(0)7908-314-155, Cressida_Robson@eisai.net,
Charlotte_andrews@eisai.net ; Tonic Life Communications: Siobhan Reilly /
Nicola Lilley, +44(0)207-798-9999 / +44(0)207-798-9905,
Siobhan.reilly@toniclc.com, eisaiepilepsy@toniclc.com
 
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