First Presentation of Pooled Phase III Data Supporting Europe's Newest Partial Epilepsy Treatment

HATFIELD, England, October 4, 2012 /PRNewswire/ --

New results for Fycompa^® (perampanel) presented today at leading epilepsy conference

New data shared today with Europe's epilepsy community at the 10th European Congress on Epileptology (ECE) in London, demonstrate the efficacy of once-daily Fycompa^® (perampanel) in reducing partial-onset seizures, the most common form of epilepsy, and its effectiveness and flexibility of use as add-on therapy.

The successful treatment of partial-onset seizures (the most common form of epilepsy) remains a significant challenge in some patients and the incidence of uncontrolled partial epilepsy remains high, despite many existing anti-epileptic drugs (AEDs); between 20 - 40% of patients with epilepsy have remained poorly controlled despite these treatments.^[1] The new data supports the use of perampanel as a new therapeutic option for this hard-to-treat patient population.

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.^[2] In addition, the results show that perampanel decreased the frequency of both complex partial seizures and secondarily generalised seizures.^[3] 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.^[4]

"This first-ever presentation of the pooled data from the perampanel Phase III trial programme has been anticipated by the epilepsy community. These results complement to the wealth of efficacy and safety data from the clinical development programme supporting the use of the new treatment. In addition, they further demonstrate the important adjunctive role that perampanel may have in the treatment of patients with partial onset seizures in Europe," commented Professor Bernhard Steinhoff Medical Director and Executive at the Epilepsy Centre, Kehl-Kork, Germany.

Specific results from the three new analyses include:

• Abstract 656; E. Ben-Menachem et al.:^[2] 1,265 patients (348, 161, 159, 46, 287, 14, 114) patients were included in the safety population for placebo, perampanel 2, 4, 8, 12 mg (randomized dose). Median percent changes in seizure frequency for placebo, 2, 4, 8, 12 mg were -11.7%, -17.3%, -24.1%, -31.9%, -26.2%, respectively. Responder rates were 18.4%, 22.4%, 30.8%, 37.6%, and 39.5%. These data are comparable with randomized results from the individual studies, which did not account for failure to reach assigned doses. Safety analyses were also comparable.
• Abstract 417; B.J. Steinhoff et al.:^[3] 442, 180, 172, 431, and 254 patients were randomised to placebo, perampanel 2, 4, 8, 12 mg, respectively. Median percent changes in CPS+SGS frequency were -14.6% (n=319), -26.6% (n=150), -35.6% (n=145), -35.9% (n=267), -30.3% (n=104) for placebo, perampanel 2, 4, 8, 12 mg actual doses. Responder rates were 21.9%, 29.3%, 37.9%, 40.1%, 39.4%. Median percent changes in SGS frequency were -19.5% (n=133), -27.9% (n=60), -54.6% (n=66), -60.8% (n=112), -56.0% (n=43) for placebo, 2, 4, 8, 12 mg. Responder rates were 38.3%, 43.3%, 53.0%, 56.3%, 53.5%
• Abstract 669; E. Trinka et al.:^[4] Median changes from baseline in seizure frequency for the five most common concomitant AEDs in the pooled perampanel Phase III studies are provided for placebo, 4, 8, 12 mg, respectively. Carbamazepine: -13% (n=128), -24% (n=49), -30% (n=116), -18% (n=65);  valproate: -18% (n=128), -28% (n=69), -31% (n=94), -26% (n=31); lamotrigine: -13% (n=112), -25% (n=64), -33% (n=113), -37% (n=36); levetiracetam: -18% (n=116), -19% (n=46), -31% (n=92), -39% (n=46); oxcarbazepine: -5% (n=80), -36% (n=24), -32% (n=54), -38% (n=21). 50% responder rates for each of the AEDs were generally consistent with the median percent changes.

Discovered and developed by Eisai in Europe and Japan, perampanel is the first and only licensed AED in Europe with a mode of action that selectively targets AMPA receptors, which are thought to play a central role in seizure generation and spread.^[5]  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,^[6] and it is the only contemporary epilepsy treatment approved for adolescents from launch which can lead to earlier seizure control in younger patients.

The European Commission's (EC) Marketing Authorisation Approval of perampanel was based on three global pivotal Phase III studies with 1,480 subjects. These  randomised, double-blind, placebo-controlled, and dose-escalated  studies showed consistent results in the efficacyand tolerability of perampanel as an adjunctive therapy in patients with partial-onset seizures (with or without secondary generalisations).^[7],[8],[9] The most commonly reported adverse events were dizziness, headache, somnolence, irritability, fatigue, falls, and ataxia.^[7],[8],[9]

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.

Notes to Editors

About Perampanel

Perampanel is licensed in Europe Union as an adjunctive treatment for people aged 12 years and older with partial-onset seizures, with or without secondarily generalised seizures.^[6]

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.^[6]

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

About Abstract 656^[2]

Patients (≥12 years with uncontrolled partial-onset seizures) were randomised to double-blind placebo or perampanel at doses 2, 4, 8 or 12 mg/day. Percent change in seizure frequency/28 days and 50% responder rate were primary endpoints. Efficacy analyses in this report were based on actual (last) doses received at the end of the double-blind phase by completer patients (excluding Central/South American patients due to significant treatment-by-region interactions). Safety analyses included all treated patients who had safety assessments. 348, 161, 159, 46, 287, 14, 114 patients completed the study on a last dose of placebo, perampanel 2, 4, 6, 8, 10, 12 mg.

About Abstract 417^[3]

Following baseline, patients were randomised to once-daily placebo, perampanel 2, 4, 8, or 12 mg. Endpoints included percent change in CPS+SGS and SGS frequency/28 days (vs baseline), and CPS+SGS and SGS 50% responder rates. Analyses were based on last actual perampanel doses in patients completing 19 weeks' treatment (excluding Central/South American patients due to significant treatment-by-region interactions).1,264 patients completed the studies and numbers of patients achieving each actual dose were: 348, 161, 159, 46, 287, 14, 114 for placebo, perampanel 2, 4, 6, 8, 10, 12 mg.

About Abstract 669^[4]

Patients ≥12 years experiencing treatment-resistant partial-onset seizures despite 1-3 concomitant AEDs were randomized to once-daily, double-blind placebo or perampanel (2, 4, 8 or 12 mg). Analysis of the median percent reduction from baseline in seizure frequency/28 days by last dose in patients who completed the maintenance period (actual dose analysis) was performed for patients concomitantly receiving carbamazepine [n=428], valproate [n=419], lamotrigine [n=397], levetiracetam [n=370], or oxcarbazepine [n=233], as part of their regimen.

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, Africa and Russia (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)
• Zebinix^® (eslicarbazepine acetate) as adjunctive therapy in adult patients with partial-onset seizures, with or without secondary generalisation. (Zebinix is under license from BIAL)
• 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 recently expanded their UK Hatfield commercial, research and manufacturing facility which now supports the company's growing EMEA business.

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 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, Slovakia, the Netherlands, Belgium, Luxembourg, the Middle East and Russia.

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

References

1. French JA. Refractory Epilepsy; Clinical Overview. Epilepsia 2007: 48 (Suppl1) 3 - 7

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

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

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

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

6. Fycompa Summary of Product Characteristics. 2012

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

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

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

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

11. Pugliatti M, et al. Epilepsia 2007: 48(12) 2224 - 2233.

Job code: Perampanel-UK2095 Date of preparation: October 2012