Eisai Disagrees with German Institute for Quality and Efficiency in Health Care (IQWiG) Report on Innovative Antiepileptic Drug Fycompa® (Perampanel) for the Treatment of Partial Epilepsy

HATFIELD, England, December 18, 2012 /PRNewswire/ --

In the assessment report by the Institute for Quality and Efficiency in Health Care (IQWiG) on Fycompa® (perampanel), published today on the Federal Joint Committee (G-BA) website, the institute did not attest an additional benefit. Comments on the report and its proposed conclusion can be submitted to the G-BA up until 07 January 2013. The G-BA will decide on the additional benefit in March 2013 after reviewing comments and the discussion from an oral hearing of experts end of January. The current IQWiG assessment has no implications on the reimbursement of perampanel or doctors' ability to prescribe this new partial epilepsy treatment.

Eisai today expressed its strong disappointment with IQWiG in regards to their assessment of the additional benefit, of the new epilepsy treatment perampanel compared to a treatment defined by the G-BA. It is reported that additional benefit is unproven based on methodological considerations.^[1] No statement was made regarding clinical efficacy and safety. Perampanel is the first in an entirely new class of treatment for uncontrolled partial epilepsy with a novel mechanism of action that is different from all other anti-epileptic drugs (AEDs). The company believes that, while discussing at length methodological aspects of analyses, IQWiG failed to adequately interpret the patient-relevant benefits and responsibly recognise the innovative nature of the new drug in a clinical setting with a high unmet need.

Perampanel is indicated as an adjunctive treatment for partial seizures (the most common form of epileptic seizures), with or without secondarily generalised seizures, in patients with epilepsy aged 12 years and older.^[2] It was first launched in Europe in Germany and the UK in September 2012 and has been well received by both patients and doctors. It is the first and only licensed AED to selectively target AMPA receptors which play a critical role in causing seizures.^[3] It blocks the effects of glutamate, which can trigger and maintain seizures.

"We believe we provided compelling evidence of the additional benefit of perampanel based on the advice received by the G-BA. By taking a negative view, IQWiG ignores the therapeutic value that this first-in-class new AED brings to the real-life clinical setting. There still remains a very high need for new drugs to reduce seizures in patients with refractory partial epilepsy," points out Franz Wetzel, Epilepsy Business Unit Director, Eisai Germany. "In addition, perampanel has the further benefit of convenient, once-daily dosing at bedtime and it is the only new-generation partial epilepsy treatment approved to treat adolescents with epilepsy from launch."

Nick Burgin, European Director of Market Access, Eisai added; "We are dismayed by this critical assessment of perampanel. Even while facing measures to cut costs in the current economic climate it remains important to consider the pressing needs of the patients for new, innovative medicines. Eisai will make all efforts to have available data adequately considered in order to achieve recognition of the resulting additional benefit.

An estimated 500.000 - 650.000 people with epilepsy live in Germany.^[4] Epilepsy is one of the most common neurological conditions in the world.^[5] The successful treatment of partial-onset seizures remains a challenge. Up to 30% of patients with partial-onset seizures do not achieve seizure freedom despite appropriate therapy with anti-epileptic drugs.^[6]

Perampanel was approved by the European Commission on 23 July 2012 and is currently available in the UK, Denmark, Germany, Austria and Sweden. Swissmedic, the Swiss Agency for Therapeutic Products approved perampanel for use on 17 December 2012. The FDA approved perampanel for use in the US on 22 October 2012.

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 as an adjunctive treatment for people aged 12 years and older with partial-onset seizures, with or without secondarily generalised seizures.^[2]

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 signaling including epilepsy, neurodegenerative disorders, movement disorders, pain and psychiatric disorders.^[2]

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.^[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.

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. Dossierbewertung A12-12 Version 1.0 Perampanel - Nutzenbewertung gemäß § 35a SGB V 13.12.2012

2. Fycompa. Summary of Product Characteristics. August 2012

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

4. Pfäfflin, M. Epidemiologie der Epilepsien (online). 2011 URL: http//www.izepilepsie.de/home/showdoc.id.387.aid.4163.html.

5. 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)

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

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 2007: 48(12);2224-2233

Date of preparation: December 2012

Job code: Perampanel - UK2118