New First-In-Class Treatment Fycompa® (Perampanel) Approved In Switzerland For Partial Epilepsy

HATFIELD, England, January 8, 2013 /PRNewswire/ --

Fycompa^® (perampanel), the first in an entirely new class of treatment for uncontrolled partial epilepsy (the most common form of the condition), is approved today by Swissmedic, the Swiss agency for the authorisation and supervision of therapeutic products. The new therapy is indicated as an adjunctive treatment for partial-onset seizures, with or without secondary generalised seizures, in people with epilepsy aged 12 years and older.^[1]

Perampanel is the first and only licensed anti-epileptic drug (AED) to selectively target AMPA receptors, a protein in the brain which plays a critical role in causing seizures.^[2] This mechanism of action is different to other, currently available AEDs. In addition, perampanel has the added benefit of convenient, once-daily dosing at bedtime^[1] and, significantly, is the only new-generation partial epilepsy treatment approved to treat adolescents with epilepsy from launch.

"The approval of Fycompa by Swissmedic is very good news for both doctors and patients as the new drug provides a valuable new option for the treatment of partial-onset epilepsy. Uncontrolled seizures can severely impact patient quality of life and this new treatment may potentially help people in Switzerland achieve better seizure control," commented Dr Med Guenter Kraemer, Medical Director, Swiss Epilepsy Centre. "In addition, Fycompa has the added benefit of once daily dosing, which may optimise adherence in patients already taking other medicines."

An estimated 70,000 people live with epilepsy in Switzerland.^[3] Epilepsy is one of the most common neurological conditions in the world.^[4] 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.^[5]

Perampanel's approval by Swissmedic 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 people with partial-onset seizures (with or without secondary generalisations).^[6][7][8] The most commonly reported adverse events were dizziness, somnolence, fatigue, headache, falls, irritability and ataxia. ^[6][7][8] Perampanel was approved by the European Commission on 23 July 2012 and is currently available in the UK, Denmark, Germany, Sweden and Austria. The FDA approved Fycompa for use in the US on 22 October 2012.

Discovered and developed by Eisai in Europe and Japan, and is going to be manufactured in the UK. 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.^[9]  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,^[10]  and it is the only contemporary epilepsy treatment approved for adolescents from launch which can lead to earlier seizure control in younger patients.

The development of perampanel underscores Eisai's human health care (hhc) 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. Eisai is proud to currently market more epilepsy products in Europe, the Middle East, Africa and Russia (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.^[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, neurodegenerative disorders, movement disorders, pain and psychiatric disorders.^[1]

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

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 12 mg (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.^[11] In addition, the results show that perampanel decreased the frequency of both complex partial seizures and secondarily generalised seizures.^[12] 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.^[13]

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^[6] was to identify the minimal effective dose and included four treatment arms (placebo, 2mg, 4mg, and 8mg). Study 304^[7] and Study 305^[8] 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.^[14],[15] 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). 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 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. Fycompa. Summary of Product Characteristics. November 2012

2. Rogawski MA. Revisiting AMPA receptors as an antiepileptic drug target. Epilepsy Currents 2011;11:56-63

3. EPI Swiss Epilepsy Centre. Available at: http://www.swissepi.ch/web/swe.nsf/swe__swebasdocs/epi_klinik_kurzinfo_englisch?OpenDocument (Accessed August 2011)

4. ILAE/IBE/WHO, Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe 2010. Available at; http://www.ilae-epilepsy.org/Visitors/Documents/EUROReport160510.pdf (Accessed June 2011)

5.  Kwan P, Brodie MJ Early identification of refractory epilepsy. New England Journal of Medicine 2000; 342:314-9

6.  Krauss GM. Serratosa JM, Villanueva V et al. Neurology 2012: Available at: http://www.neurology.org/ 7.  French JA. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology 2012;79:589-596

8.  French JA et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: Results of randomized global phase III study 305. Epilepsia 2012:1-9. In press online

9. Rogawski MA. Revisiting AMPA receptors as an antiepileptic drug target. Epilepsy Currents 2011;11:56-63

10. Fycompa Summary of Product Characteristics. November 2012

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

12. Steinhoff BJ, Gauffin H, McKee P et al. Abstract presented at ECE 201213. Trinka E, Straub H, Squillacote D et al. Abstract presented at ECE 2012

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

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

15  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: January 2013
Job code: Fycompa-EU0017