All Wales Medicines Strategy Group (AWMSG) Approves Fycompa® (Perampanel) as Once Daily Partial Epilepsy Treatment

HATFIELD, England, August 7, 2013 /PRNewswire/ --

Treatment approved for patients whose seizures are still uncontrolled with first adjunctive therapy

The All Wales Medicines Strategy Group (AWMSG) has issued a Final Appraisal Recommendation (FAR) on the anti-epilepsy (AED) drug Fycompa (perampanel).  Fycompa has been approved for use in Wales for the treatment of partial-onset seizures, with or without secondarily generalised seizures, for patients aged 12 years and older whose seizures remain uncontrolled with first adjunctive therapy.^[1]  It is the first in an entirely new class of treatment for uncontrolled partial epilepsy, the most common form of the condition.

Epilepsy affects approximately 32,000 people in Wales.^[2] The successful treatment of partial-onset seizures remains a significant challenge and the incidence of uncontrolled partial epilepsy remains high as between 20 - 40% of patients with epilepsy have remained poorly controlled despite many existing anti-epileptic drugs.^[3]

Nick Burgin, Director Market Access, Eisai EMEA & Russia explained: "We are delighted that the AWMSG has recognised the innovative nature of Fycompa and the potential benefit it can bring to people in Wales in its new appraisal process.  We want to ensure that patients have access to new treatments and thereby encourage better patient outcomes, in particular improved seizure control."

"The approval of perampanel by the AWMSG is a welcome decision. It could prove to be an effective treatment for those people who still live with uncontrolled seizures despite taking epilepsy medication. Seizures can have a huge impact on people's quality of life. It is encouraging that people in Wales will be able to access a new treatment which could lead to more people gaining improved seizure control,"commented Ann Sivapatham, Epilepsy Action's Wales Manager.

Discovered and developed by Eisai in the UK and Japan, perampanel is the first and only approved 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.^[4]  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,^[5] and it is the only third generation epilepsy treatment approved for adolescents.

Perampanel was approved by the European Commission (EC) in July 2012. The EC's 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).^[6],[7],[8] The most commonly reported adverse events were dizziness, headaches, 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 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. ^[5]

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. Perampanel is licensed for the adjunctive treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy.

The Scottish Medicines Consortium (SMC) approved perampanel as a second-line adjunctive treatment in patients with refractory partial onset epilepsy i.e. patients who have previously received monotherapy and are not seizure free after at least one other adjunctive therapy.

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.^[9],[10] In addition, the results show that perampanel decreased the frequency of both complex partial seizures and secondarily generalised seizures.^[10] 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.^[11]

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^[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.^[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 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 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, Africa and Russia (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, the Middle East and Russia.

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

References

1. AWMSG Final Appraisal Recommendation http://www.awmsg.org/awmsgonline/app/appraisalinfo/1219

2. Joint Epilepsy Council. http://www.jointepilepsycouncil.org.uk/downloads/2011/Joint%20Epilepsy%20Council%20Prevalence%20and%20Incidence%20September%2011.pdf

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

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

5. Fycompa Summary of Product Characteristics. 2012

6. Krauss G L et al. Neurology 2012; 78: 1408-1415.

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

8. French J A et al.Epilepsia 2012. Article in press

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

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

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

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

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

Date of preparation: August 2013
Job Code: Perampanel-UK2124