New First-in-class Epilepsy Treatment Fycompa® (perampanel) Approved In Israel

HATFIELD, England, October 22, 2013 /PRNewswire/ --



Fycompa^® (perampanel), the first in an entirely new class of treatment for uncontrolled partial-onset seizures (the most common form of epilepsy) is approved in Israel. 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] In Israel, perampanel will be launched and marketed by Megapharm, Eisai's local CNS partner.

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.

"We are proud to be Eisai's partner for the Israeli pharmaceutical market," commented Miron Drucker, CEO of Megapharm. "We are excited about the impending launch of Fycompa. It will bolster our strong position in the epilepsy and CNS market and provide patients and doctors in Israel with an important new treatment option that has already proved useful in other parts of the world. Fycompa also adds to our growing portfolio of Eisai products in other therapeutic areas."

Epilepsy is one of the most common neurological conditions in the world^[3] and affects an estimated 50 million people worldwide.^[4] 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.^[5] Effective seizure management therefore remains a challenge. Uncontrolled seizures can impact severely a patient's quality of life and there is a need to provide these people with new treatment options that may help to manage their condition.  

The approval of perampanel in Israel was based on three global pivotal Phase III studies involving 1,478 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 in Europe the drug is currently available in the United Kingdom, Denmark, Germany, Republic of Ireland, Sweden, Norway, Austria and Switzerland. The United States Federal Drug Administration (FDA) approved perampanel for use in the US on 22 October 2012. Discovered and developed by Eisai in Europe and Japan, perampanel is manufactured in the UK.

The launch of perampanel in Israel by Megapharm 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 wellbeing 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.

Notes to Editors

About Perampanel

Perampanel is licensed in the European Union (EU) 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.^[1]

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

About the Perampanel Pooled Data (Study 306, 305 and 304)^[6],[7],[8]

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.^[9]

50% 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.^[9] 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]

Perampanel was generally well tolerated; most adverse events were mild/moderate.

About 307^[12]

The 307 study (n=1,218) was designed to evaluate safety, tolerability, and seizure outcome data during long-term treatment with once-daily adjunctive perampanel (up to 12 mg/day) in people with refractory partial onset seizures. It was an open-label extension (OLE) study for people completing the double-blind phase of three pivotal Phase III trials (studies 304, 305, and 306).  

The study consisted of two phases: an open-label treatment phase (including a 16-week conversion period and a planned 256-week maintenance period) and a 4-week follow-up phase. People were blindly titrated during the Conversion Period to their individual maximum tolerated dose (maximum 12 mg/day). Adverse events (AEs) were monitored throughout the study and seizure frequency recorded. The interim data cut-off date for analyses was 1 December 1 2010.

At the interim cut-off date, 1186 patients were in the safety analysis set; 1089 (91.8%) patients had >16 weeks' exposure to perampanel, 580 (48.9%) patients had >1 year of exposure, and 19 (1.6%) patients had >2 years' exposure. At the interim analysis, 840 (70.8%) patients remained on perampanel treatment. The large majority of patients (n=1084 [91%]) were titrated to 10 mg or 12 mg/day.  Median (range) duration of exposure was 51.4 (1.1-128.1) weeks.  

In the ITT analysis set (n=1207), the frequency of all seizures decreased over the first 26 weeks of perampanel treatment in patients with at least 26 weeks' exposure to perampanel (n=1006 [83.3%]); this reduction was maintained in patients with at least one year of exposure (n=588 [48.7%]). The overall median percent changes in seizure frequency in patients included in each 13-week interval of perampanel treatment were -39.2% for weeks 13-26 (n=1114), -46.5% for Weeks 40-52 (n=731), and 58.1% for Weeks 92-104 (n=59). Overall responder rates in patients included in each 13-week interval of perampanel treatment were 41.4% for Weeks 13-26 (n=1114), 46.9% for Weeks 40-52 (n=731) and 62.7% for weeks 92-104 n=59).  During the blinded conversion period, the reduction in seizure frequency in patients previously randomised to placebo (-42.4%, n=369) was similar to that in patients previously randomised to perampanel (-41.5%, n=817).

Treatment-emergent AEs were reported in 87.4% of patients. The most frequent were dizziness (43.9%), somnolence (20.2%), headache (16.7%), and fatigue (12.1%). Serious AEs were reported in 13.2% of patients.

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 worldwide.^[13],[14] In Israel an estimated 52,000 people live with the condition.^[4] Epilepsy is a chronic disorder of the brain that affects people of all ages. It is characterised by abnormal discharges of neuronal activity which causes 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 EMEA 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, Russia and Oceania (EMEA).

In the EMEA region, Eisai currently has four marketed treatments including:

• Zonegran^® (zonisamide) as monotherapy and adjunctive therapy in adults, adolescents and children aged six years and above* 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. (Rufinamide was originally developed by Novartis)
• 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 and we define our 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 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 EMEA Knowledge Centre in Hatfield, UK, Eisai has recently expanded its business operations to include Europe, the Middle East, Africa, Russia and Oceania (EMEA). Eisai EMEA has sales and marketing operations in over 20 markets, including the United Kingdom, Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Ireland, Italy, Norway, Portugal, Russia, Slovakia, Spain, Switzerland, Sweden, the Netherlands and the Middle East.

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

About Megapharm

Megapharm Ltd. is one of the leading private biotech, pharmaceutical and medical nutrition marketing companies in Israel with a strong biotech orientation, exclusively representing a number of major American and European pharmaceutical companies. Megapharm has demonstrated dynamic sales growth by developing a strong company presence and expertise in select therapeutic areas and diversified segments of the healthcare business.

For more information see http://www.megapharm.co.il.

References

1. Fycompa. Summary of Product Characteristics.(updated November 2012) [Accessed 22 July 2013]

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

3. 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 Feb 2013)

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

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

6. Krauss GM. et al. Randomized phase III study 306: Adjunctive perampanel for refractory partial-onset seizures. Neurology 2012; 78:1408-1415

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

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. Krauss GL et al. Perampanel, a selective, noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, as adjunctive therapy for refractory partial-onset seizures: interim results from phase III, extension study 307. Epilepsia, 2013;54(1):126-34

13. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf [Accessed 18 July 2012].

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

Date of preparation: October 2013
Job code: perampanel-UK2141