Real World Data to be Presented for Fycompa® (Perampanel) at the European Congress on Epileptology (ECE) 2014

  Real World Data to be Presented for Fycompa® (Perampanel) at the European
                     Congress on Epileptology (ECE) 2014

  PR Newswire

  HATFIELD, England, June 30, 2014

HATFIELD, England, June 30, 2014 /PRNewswire/ --

   Further analyses of pivotal Phase III data for perampanel  will also be
                      presented for first time at ECE 

Real world data for Fycompa ^® (perampanel) have been published in 10
abstracts in Epilepsia and will be presented for the first time this week at
the XXI European Congress on Epileptology (ECE) in Stockholm, Sweden. In
addition, subset data from the Phase III pivotal trials of perampanel will be
unveiled at the congress. Perampanel is indicated for the adjunctive treatment
of partial onset seizures, with or without secondarily generalised seizures,
in patients with epilepsy aged 12 years and older. ^[1]

The 10 Eisai-supported observational studies evaluate real world experience
with adjunctive perampanel in over 350 refractory patients across sites in the
UK and Austria. ^[2]-[11] The data show perampanel as generally effective and
well tolerated in a variety of patient populations, including those with
highly refractory epilepsy and those with a high number of comorbidities.

In two further abstracts, metabolic parameters were assessed for the
perampanel pooled Phase III global pivotal studies (n=1,480) ^[12] and an
open-label extension study (n=1,186). ^[13] Results show that lipid parameters
(blood cholesterol and triglyceride levels) and glucose levels remain stable
over time across a range of doses (up to 12mg per day) of perampanel. The most
common metabolic treatment emergent adverse event reported for both studies
was weight increase. ^[12],[13]

A study that assessed the impact of perampanel on behaviour in adolescents
with refractory partial onset seizures (12-17 years old, n=133) is the subject
of an additional abstract at ECE. ^[14]

"Data such as these add to the growing weight of evidence that supports the
use of perampanel for adults and adolescents with refractory epilepsy.
Treatments, such as perampanel, that have proven efficacy and an entirely
different mode of action compared to other anti-epileptic drugs are an
important adjunctive therapy option," commented Christoph Baumgartner,
Neurological Center Rosenhuegel and General Hospital Hietzing, Vienna.

Perampanel is the only licensed anti-epileptic drug (AED) to selectively
target AMPA receptors, a protein in the brain which plays a critical role in
the spread of seizures. ^[15] Perampanel has the added benefit of convenient,
once-daily dosing at bedtime ^[1] and, significantly, is the only
new-generation partial onset epilepsy treatment approved to treat adolescents
(>12 years) from launch.

The data presented at ECE underscore Eisai's human health care (hhc) mission;
the company's commitment to provide innovative solutions in disease
prevention, cure and care for the health and wellbeing of people worldwide.
Eisai is proud to currently market more epilepsy products in EMEA than any
other company.

Notes to Editors 

About Fycompa ^®  (perampanel) 

Perampanel is indicated for the adjunctive treatment of partial onset
seizures, with or without secondarily generalised seizures, in patients with
epilepsy aged 12 years and older. ^[1]

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. ^[1]

Further information for healthcare professionals can be found at
http://www.fycompa.eu 

About the Perampanel Pooled Data ^[16] 

The main objective of the pooled analysis of the results of the three Phase
III studies (304 ^[17] , 305 ^[18] and 306 ^[19] ) was to compare the efficacy
and tolerability of perampanel, administered in one daily dosage with that of
the placebo in combination therapy in patients aged 12 and above with partial
seizures uncontrolled by one to three AEDs. The primary efficacy endpoint of
the three studies for EU registration was the rate of responders (defined as
the percentage of patients achieving a reduction in the frequency of all
partial onset seizures by at least 50% for a period of 28 days of treatment).


The data from each efficacy end point 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), 305 (n=386) and 306 (n=705).

The results of the pooled analysis showed that median reductions in partial
seizure frequency were greater with perampanel 4mg (-23·3%), 8 mg (-28·8%),
and 12mg (-27·2%) than placebo (-12·8%; p<0·01, each dose vs. placebo). 50%
responder rates were greater with perampanel 4mg (28·5%), 8mg (35·3%), and
12mg (35·0%) than placebo (19·3%; p<0·05, each dose vs. placebo). Median
reductions in complex partial and secondary generalized seizure frequency were
greater with perampanel 4mg (-31·2%), 8mg (-35·6%), and 12mg (-28·6%) than
placebo (-13·9%). Perampanel was generally well tolerated with most adverse
events being mild or moderate.

About Study 307 ^[20] ^

The Phase III open-label extension study (n=1,218) of patients from pivotal
trials ^[17], ^[18], ^[19] was designed to evaluate safety, tolerability, and
seizure outcome data during long-term treatment with once-daily adjunctive
perampanel in people with refractory partial onset seizures.

Patients aged ≥12 years with partial-onset seizures despite treatment with one
to three antiepileptic drugs at baseline completed a perampanel Phase III
trial and entered extension study 307 (NCT00735397). Patients were titrated to
12mg/day (or their individual maximum tolerated dose) during the blinded
conversion period, followed by open-label maintenance. Exposure, safety
(adverse events, vital signs, weight, electrocardiography [ECG], laboratory
values) and seizure outcomes were analysed; key measures were assessed by
geographic regions.

Results show that after titration/conversion, responder rate and median
percentage change from baseline in seizure frequency were stable for
perampanel: 46% for both measures at nine months (in 980 patients with ≥9
months' exposure) and 58% and 60%, respectively, at two years (in the 337
patients with 2 years' exposure). In patients with at least two years
perampanel exposure and secondary generalised seizures at baseline (n=141), an
up to 90% reduction in secondary generalised seizures was observed. Among the
694 patients with maintenance data for at least one year, 5.3% were
seizure-free for the entire year.

The study showed that among 1,216 patients perampanel was well tolerated up to
3.3 years at a median daily dose of 10.6 mg/day. The most frequent adverse
events reported in ≥10% of patients were dizziness, somnolence, headache,
fatigue, irritability and weight increase. Only dizziness and irritability
caused discontinuation from the study in >1% of patients (3.9% and 1.3%,
respectively).

Safety and seizure responses were similar across a large number of
geographical regions and ethnicities (249 centres in 39 countries), with high
treatment retention at the study end (average 58.5%).

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 worldwide. ^[12],[13] Epilepsy is a chronic disorder of the
brain that affects people of all ages. It is characterised by abnormal
discharges of neuronal activity which causes 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 EMEA 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,
Africa, Russia and Oceania (EMEA).

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

  *Fycompa ^® (perampanel) for the adjunctive treatment for partial onset
    seizures, with or without secondarily generalised seizures, in patients
    with epilepsy aged 12 years and older
  *Zonegran ^® (zonisamide) as monotherapy in the treatment of partial
    seizures, with or without secondary generalisation, in adults with newly
    diagnosed epilepsy and as adjunctive therapy in the treatment of partial
    seizures, with or without secondary generalisation, in adults,
    adolescents, and children aged 6 years and above (Zonegran is under
    license from the originator Dainippon Sumitomo Pharma)
  *Zebinix ^® (eslicarbazepine acetate) as adjunctive therapy in adults with
    partial onset seizures, with or without secondary generalisation (Zebinix
    is under license from BIAL)
  *Inovelon ^® (rufinamide) for the adjunctive therapy in the treatment of
    seizures associated with Lennox-Gastaut syndrome (LGS) in patients four
    years of age and older (Rufinamide was originally developed by Novartis)

About Eisai 

Eisai is one of the world's leading research and development (R&D) based
pharmaceutical companies and we define our 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 R&D activities in three key areas:

  *Neuroscience, including: Alzheimer's disease, epilepsy, pain and weight
    management
  *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 EMEA
Knowledge Centre in Hatfield, UK, Eisai has recently expanded its business
operations to include Europe, the Middle East, Africa, Russia and Oceania
(EMEA). Eisai EMEA has sales and marketing operations in over 20 markets,
including the United Kingdom, Austria, Belgium, Czech Republic, Denmark,
Finland, France, Germany, Ireland, Italy, Norway, Portugal, Russia, Slovakia,
Spain, Switzerland, Sweden, the Netherlands and the Middle East.

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

References 

1.Fycompa, Summary of Product Characteristics (updated November 2013):
    http://www.medicines.org.uk/emc/medicine/26951/ [
    http://www.medicines.org.uk/emc/medicine/26951 ] 
2.Philip S et al. Efficacy and tolerance of perampanel in pharmacoresistant
    epilepsy in children and young people. Abstract presented at ECE 2014.
    P126 
3.Sieradzan K et al. Efficacy and tolerability of perampanel in patients
    with refractory partial epilepsy in a tertiary epilepsy centre. Abstract
    presented at ECE 2014. P137 
4.Parrett M et al. A service evaluation of perampanel in Cornwall. Abstract
    presented at ECE 2014. P334  
5.Flynn C et al. Seizure response to perampanel in a severe refractory group
    of epilepsy patients. Abstract presented at ECE 2014. P343  
6.Manidakis I et al. Perampanel in the treatment of epilepsy; a multicentre
    evaluation. Abstract presented at ECE 2014. P562  
7.Geldard J et al. A service evaluation of perampanel (Fycompa) at Leeds
    General Infirmary. Abstract presented at ECE 2014. P335  
8.Coyle H et al. Clinical experience with perampanel in a regional epilepsy
    clinic. Abstract presented at ECE 2014. P563  
9.Lawthom C et al. Perampanel in South Wales: A multi-centre clinical
    evaluation. Abstract presented at ECE 2014. P138  
10.Kelly K et al. Adjunctive perampanel in highly drug-resistant
    localization-related epilepsy - a prospective audit. Abstract presented at
    ECE 2014. P119  
11.Baumgartner C et al. First clinical experiences with perampanel in Vienna.
    Abstract presented at ECE 2014. P573 
12.Brodie MJ et al. Evaluation of metabolic parameters over time in the
    perampanel pooled Phase III epilepsy studies.Abstract presented at ECE
    2014. 009  
13.Patsalos PN et al. Effects of perampanel on metabolic parameters in
    patients with refractory partial-onset seizures in extension study 307.
    Abstract presented at ECE 2014. 010
14.Lagae L et al . Impact of adjunctive perampanel on behaviour in
    adolescents with refractory partial-onset seizures. Abstract presented at
    ECE 2014. P558  
15.Rogawski MA. Revisiting AMPA receptors as an antiepileptic drug target.
    Epilepsy Currents 2011:11:56-63
16.Steinhoff B et al . Efficacy and safety of adjunctive perampanel for the
    treatment of refractory partial seizures: a pooled analysis of three Phase
    III studies. Epilepsia 2013:54(8):1481-9
17.French JA et al . Adjunctive perampanel for refractory partial-onset
    seizures: randomized phase III study 304.Neurology 2012:79(6):589-596
18.French JA et al . Evaluation of adjunctive perampanel in patients with
    refractory partial-onset seizures: Results of randomized global phase III
    study 305. Epilepsia 2013:54(1):117-125
19.Krauss GM et al . Randomized phase III study 306: Adjunctive perampanel
    for refractory partial-onset seizures. Neurology 2012:78(18):1408-1415
20.Krauss GL et al. Long-term safety of perampanel and seizure outcomes in
    refractory partial-onset seizures and secondarily generalised seizures:
    Results from Phase III extension study 307. Epilepsia 2014; DOI:
    10.1111/epi.12643 (available at
    http://onlinelibrary.wiley.com/doi/10.1111/epi.12643/pdf )
21.Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe.
    http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf (Accessed
    June 2014)
22.Pugliatti M et al . Estimating the cost of epilepsy in Europe: A review
    with economic modeling. Epilepsia 2007:48(12):2224-2233.

Date of preparation: June 2014 Job code: perampanel-UK2160



Contact: Media Enquiries, Eisai Europe Ltd, Cressida Robson/Ben Speller,
+44(0)7908-314-155/+44(0)7908-409416, Cressida_Robson@eisai.net,
Ben_Speller@eisai.net ; Tonic Life Communications, Frances Murphy/Nicola
Lilley, +44(0)207-798-9262 /+44(0)207-798-9905, frances.murphy@toniclc.com,
nicola.lilley@toniclc.com
 
Press spacebar to pause and continue. Press esc to stop.