Eisai Appalled by the German Federal Joint Committee's Decision on Innovative Antiepileptic Drug Fycompa® (perampanel)

FRANKFURT, Germany and HATFIELD, England, March 7, 2013 /PRNewswire/ --

The German Federal Joint Committee (G-BA), the decision-making body of the self-governing medical system in Germany, today announced that it considers the additional benefit of Fycompa^® (perampanel) unproven when compared to two other treatments as defined by the G-BA.^[1] Perampanel is indicated as an adjunctive treatment of partial-onset seizures with or without secondarily generalised seizures in patients with epilepsy aged 12 years and older.^[2] Perampanel is the first in an entirely new class of innovative treatment for uncontrolled partial epilepsy with a novel mechanism of action that is different from all other anti-epileptic drugs (AEDs).

Eisai is appalled by the G-BA's ruling. This decision follows the German Institute for Quality and Efficiency in Health Care (IQWiG) assessment, published 17 December 2012 which reported that the benefit of perampanel is unproven based on methodological grounds. The company believes that the G-BA failed to adequately interpret the proven patient-relevant benefits substantiated in the submitted benefit dossier and to responsibly recognise the innovative nature of the new drug in a clinical setting with a highly unmet medical need.

Eisai diligently developed the benefit dossier following scientific advice from the G-BA. In addition, Eisai provided further evidence in a written statement preceding the G-BA Oral Hearing on 29 January 2013, and re-iterated the additional benefit perampanel provides to patients, especially to patients who require new options to help manage their seizures. Eisai maintains that the submitted benefit dossier contains a methodologically robust comparative analysis against the appropriate comparative therapy, lamotrigine, as defined by the G-BA. On the advice of the G-BA, Eisai also performed an indirect analysis using published clinical data for lamotrigine. Eisai strongly believes that it has provided compelling evidence to demonstrate the additional benefit of perampanel.

"I cannot understand the decision by the G-BA, from my personal clinical experience, it is definitely certain that perampanel provides additional benefit for patients with partial onset seizures. I can see this additional benefit in my clinical practice every day. There are still a large number of patients requiring new and innovative treatments like perampanel to help them manage their seizures," said Professor Bernhard Steinhoff from Epilepsiezentrum Kork, Kehl-Kork, Germany

Nick Burgin, European Director of Market Access, Eisai added; "We believe the G-BA decision failed to take into account the patient need for new innovative treatments. Further they did not acknowledge the patient-value of perampanel that was demonstrated in the comprehensive analyses submitted. This is a clear example where this process of evaluation does not reflect the additional patient benefit seen in clinical experience in an area of high unmet need."

In Germany, approximately one out of 200 people has epilepsy equating to an estimated 400,000 people in the country living with the condition.^[3] Epilepsy is one of the most common neurological conditions in the world.^[4] The successful treatment of partial-onset seizures remains a challenge as over 30% of patients do not achieve seizure freedom despite appropriate therapy with anti-epileptic drugs.^[5]

Many of these patients have exhausted other treatment options. The clinical experience with perampanel shows that it reduces the frequency of both complex partial and secondarily generalised in these difficult to treat patients.^[6]

Perampanel was first launched in Europe in Germany and the UK in September 2012. It 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.^[7] It blocks the effects of glutamate, which can trigger and maintain seizures.

Perampanel was approved by the European Commission on 23 July 2012. The FDA approved perampanel for use in the US on 22 October 2012. In Europe, it is currently available in the UK, Denmark, Germany, Austria, Sweden, Norway and Switzerland.

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 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 / http://www.fycompa.de

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.^[8] In addition, the results show that perampanel decreased the frequency of both complex partial seizures and secondarily generalised seizures.^[6] 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. http://www.g-ba.de/informationen/beschluesse/1664/ (Accessed March 2013)

2. Fycompa. Summary of Product Characteristics. August 2012

3. Pfäfflin, M. und May, T. Wieviele Patienten mit Epilepsien gibt es in Deutschland und wer behandelt sie? Neurol Rehabil, 2000; 6, (2) 77-81.

4. ILAE/IBE/WHO, Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe 2010. Available at; http://www.ilae.org/Visitors/Documents/ILAEAnnual-Report2010Final_000.pdf (Accessed June 2011)

5. Brodie MJ et al, Neurology 2012; 78:1548-1554

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

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

8. Ben-Menachem E,Krauss GL, Noachtar S 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: March 2013

Job code: Perampanel - UK2119