European Commission Approves Eisai's Fycompa® (perampanel)

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Eisai Europe Limited

26 Jul, 2012, 23:01 GMT

HATFIELD, England, July 27, 2012 /PRNewswire/ --

First region in the world to approve this new class of treatment for partial epilepsy

The European Commission (EC) has issued Marketing Authorisation Approval for the use of Fycompa® (perampanel) as an adjunctive treatment of partial-onset seizures, with or without secondarily generalised seizures, in people with epilepsy aged 12 years and older.[1] With the EC's approval, the European Union is the first region in the world to approve Eisai's perampanel.

Discovered and developed by Eisai in Europe and Japan, perampanel is currently the only approved anti-epileptic drug (AED) to selectively target AMPA receptors, which play a central role in seizure generation and spread.[2] Epileptic seizures are primarily mediated by the neurotransmitter glutamate.[3] As an AMPA receptor antagonist, perampanel selectively targets the transmission of seizures by blocking the effects of glutamate. This mechanism of action, which is different to that of current AEDs, means that perampanel is the first approved AED in this new class of treatment.[4, 5] Perampanel is the first treatment to exhibit clinical efficacy in Phase III clinical trials against partial-onset seizures by selectively (non-competitively) blocking postsynaptic AMPA receptor-mediated excitatory neurotransmission.[6, 7] The worldwide supply of perampanel will be packaged and manufactured at Eisai's EMEA (Europe, the Middle East, Africa and Russia) headquarters in Hatfield, UK. The UK will also be the first country to launch perampanel in September 2012.

"Improving seizure control is one the most pressing concerns in the care of people with epilepsy. The European approval of perampanel is exciting as it represents a completely new option for doctors to use in the fight against uncontrolled partial epileptic seizures. The epilepsy community is eagerly anticipating the availability of a new AED with unique mode of action," commented Professor Bernhard Steinhoff, Professor of Neurology, Medical Director and Executive, Epilepsy Centre, Kehl-Kork, Germany.

There are an estimated six million people living with epilepsy in Europe[8] and the successful treatment of partial-onset seizures (the most common type of epilepsy), remains a challenge for some people with epilepsy. The incidence of uncontrolled partial epilepsy remains high despite many new AEDs, and between 20 - 40% of people with newly diagnosed epilepsy will become refractory to treatment.[9]

The EC based its approval decision on clinical data from three pivotal Phase III, global, randomised, double-blind, placebo-controlled, dose-escalation studies which examined 1,480 people with partial epilepsy. Each of the studies showed consistent results in the efficacy and tolerability of perampanel as an adjunctive therapy in people with partial-onset seizures (with or without secondary generalisations).[7, 10, 11] In addition, perampanel delivers the benefit of once-daily dosing, thereby it may help to reduce the potential pill-burden a person with epilepsy may experience.[12] The most commonly reported adverse events were dizziness, headache, somnolence, irritability, fatigue, falls, and ataxia.[7, 10, 11]

Perampanel received positive opinion from the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) in May 2012. The US Food and Drug Administration (FDA) also accepted the resubmission for perampanel New Drug Application in March 2012.

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 people with epilepsy and their families. Eisai is proud to currently market more epilepsy products in EMEA than any other company.

Notes to Editors

About Perampanel

Eisai has developed perampanel for the adjunctive treatment of partial-onset seizures, with or without secondarily generalised seizures, in patients with epilepsy aged 12 years and older. 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. Perampanel is the first product in this new class for the adjunctive treatment of partial-onset seizures, with or without secondarily generalised seizures, in patients with epilepsy aged 12 years and older.

About the Perampanel Phase III studies (Study 306, 305 and 304)

The clinical development plan for perampanel consisted of three global Phase III studies: Studies 306, 305 and 304 in which a total of 1,480 patients participated. The key goal of Study 306 was to identify the minimal effective dose and included four treatment arms (placebo, 2mg, 4mg, and 8mg). Studies 304 and 305 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.

Study 306[7]- Australia, Bulgaria, China, Czech Republic, Germany, Spain, Estonia, Hong Kong, Hungary, India, Italy, South Korea, Lithuania, Latvia, Malaysia, Philippines Poland, Portugal, Romania, Russia, Serbia & Montenegro, Thailand, Taiwan and the Ukraine.

Study 306 showed that perampanel was well-tolerated and effective in reducing median seizure frequency and increasing responder rates. Specifically the results showed:

  • The 50% responder rates compared to placebo for the ITT (intention-to-treat) population were:
    2mg = 20.6% (p=ns), 4mg = 28.5% (p=0.013), and 8mg = 34.9% (p<0.001) versus 17.9% with placebo.
  • The median percent change in seizure frequency for the ITT population shown:
    2mg = -13.6% (p=0.4197), 4mg = -23.3% (p=0.003), 8mg = -30.8% (p<0.0001) versus -10.7% with placebo
  • The most frequent treatment-emergent adverse events were dizziness, somnolence and headache.

Study 305[11] - Austria, Finland, Australia, Belgium, Germany, France, Great Britain, Greece, India, Israel, Netherlands, Italy, Russia, Sweden, USA and South Africa.

The was a significant difference in median percent change in seizure frequency with perampanel 8mg and 12mg. Specifically the preliminary results for Study 305 showed:

  • The 50% responder rates compared to placebo for the ITT population were:
    8mg = 33.3% (p=0.0018), 12mg = 33.9% (p < 0.001) versus 14.7% with placebo
  • The median percent change in seizure frequency for the ITT population were:
    8mg = -30.5% (p< 0.001), 12mg = -17.6% (p=0.011) versus -9.7% with placebo
  • The most reported adverse events were dizziness, somnolence, fatigue and headache.

Study 304[10]- USA, Canada, Mexico, Chile, Argentina.

Study 304 showed consistent results in the efficacy and tolerability of perampanel given as a treatment for patients with partial-onset seizures. Specifically:

  • The 50% responder rates compared to placebo for the ITT population were:
    8mg = 37.6% (p=0.0760), 12mg = 36.1% (0.0914) versus 26.4% with placebo.
  • The median percent change in seizure frequency for the ITT population were:
    8mg = -26.3% (0.0261), 12mg = -34.5% (p=0.0158) versus -21.0% with placebo
  • The most common side effects were dizziness, somnolence, headache, falls, irritability and ataxia

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.[8, 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 three 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

About Eisai

Eisai is one of the world's leading R&D-based pharmaceutical companies and has defined its corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call human health care (hhc). 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, multiple sclerosis, neuropathic pain, epilepsy, depression
  • Oncology including: anticancer therapies; tumour regression, tumour suppression, antibodies, etc and supportive cancer therapies; pain relief, nausea
  • Vascular/Immunological reaction including: acute coronary syndrome, atherothrombotic disease, rheumatoid arthritis, psoriasis, Crohn's 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. Eisai Data on File

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

3. Meldrum BS, et al. Neurotherapeutics 2007;4:18-61.

4. Rogawski MA, et al. Nat Rev Neurosci 2004;5:553-564.

5. Brodie MJ. Seizure 2010; 19: 650-655.

6. Hanada T, et al. Epilepsia. 2011 Jul;52(7):1331-40.

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

8. 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].

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

10. French JA. Neurology 2012;79:1-1.

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

12. Cramer JA, et al. JAMA. 1989 Jun 9;261(22):3273-7.

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

Date of preparation: July 2012

Job code: Perampanel-UK2029