New Fycompa® (perampanel) Data Presented at International Epilepsy Congress (IEC)

HATFIELD, England, June 26, 2013 /PRNewswire/ --

New data provides additional evidence for use of Fycompa in partial-onset epilepsy

New data from 11 abstracts, including two oral presentations, presented at the 30^th International Epilepsy Congress (IEC) in Montreal, Canada provide additional data on the safety, efficacy and impact on quality of life (QOL) of once daily Fycompa^® (perampanel) as adjunct treatment in partial-onset epilepsy, the most common form of seizures.

One oral presentation highlighted the low discontinuation rates seen with long term perampanel treatment amongst patients who could titrate to higher doses, and a second oral presentation showed that the reduction in seizures achieved with perampanel leads to significantly improved patient QOL, even after adjusting for treatment related side effects.^[1],[2]

The first oral presentation examined the long term retention rates and the reasons for discontinuation of treatment in over 1000 patients from Phase III trials who received adjunctive perampanel treatment for 24 weeks.^[1]The results showed that the total discontinuation rates declined over time, from 7.9 % at 24-36 weeks to 2.0% at 72 weeks and this was mirrored by a decline in rates of discontinuation due to adverse events (AEs) from 2.6% at 24-36 weeks to 0.8% at 72 weeks. In the patients that discontinued treatment after 24 weeks, the most common reasons were patient choice, inadequate therapeutic effects and AEs. The investigators concluded that the pattern of discontinuation showed that patients who could titrate to higher doses tended to stay on those doses, whereas intolerant patients tended to discontinue earlier and at a lower dose.

In the second oral presentation, Phase III data from nearly 1000 patients with refractory partial epilepsy was assessed to determine the effect of seizure reduction and treatment related AEs on overall QOL.^[2] The Quality of Life in Epilepsy (QOLIE) instrument was used to show changes in quality of life over time. The results showed that reductions in seizures significantly improve QOL and decrease distress in epilepsy patients even after adjusting for side effects.

Study 307 - 10 months additional data from open-label extension study

Also presented at the IEC were additional 10 months safety and efficacy data from study 307, an open label extension sub-group study for subjects who had completed either one of the previous three double-blind Phase III clinical trials of perampanel in refractory partial-onset seizures in patients aged 12 and above.^[3],[4]

Seizure outcomes in 1090 patients in 13 week intervals in four subsets of patients ( ≥ 6, 9, 12 and 24 months of perampanel treatment) were assessed.^[3]  Most of the seizure improvement with perampanel occurred in the first 26 weeks of treatment, as the drug was up-titrated.  The responder rate (RR) was 32-35% at week 1-13 and 42-48% at weeks 14-26. Thereafter, the seizure outcomes were stable: RR ranged from 52% at week 27-39 to 58% at weeks 92-104. The patterns were similar in secondarily generalised seizures and the investigators concluded that seizure outcomes with adjunctive perampanel are stable over time up to two years of treatment.

Safety data from study 307^[4] extended the published long-term safety / tolerability data^[5] with an additional 10 months open label extension.  No new safety signals were identified in this extension study which included an analysis of 7260 additional patient-months of treatment.        

"Study 307 is a large, long term treatment trial enrolling patients from three pivotal trials and provides important long term safety and efficacy data," said Dr. Gregory Krauss, Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.

Perampanel efficacy and age

A further post-hoc study presented at IEC looked to see whether the age at the time of epilepsy diagnosis had any effect on perampanel efficacy as the risks of developing unprovoked seizures differs in childhood compared to later life.^[6] A pooled analysis of perampanel Phase III trials was carried out involving data from nearly 1500 patients aged 12 and above. The results showed that, despite differences in the baseline characteristics of patients, daily perampanel 4-12 mg demonstrated efficacy that was not related to age.

"The new data presented at IEC will further educate physicians on the efficacy and safety data from the drug's clinical development programme, and assist them in making treatment decisions for their refractory partial-onset seizure patients", pointed out David Squillacote, Eisai Global Medical Affairs, Woodcliff Lake, US."

Discovered and developed by Eisai, perampanel is the first and only licensed 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.^[7]  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,^[8] and it is the only third generation epilepsy treatment approved for adolescents from launch which can lead to earlier seizure control in younger patients.    

Notes for editors:

About perampanel

Perampanel is licensed in the European Union (EU) and Switzerland as an adjunctive treatment for people aged 12 years and older with partial-onset seizures, with or without secondarily generalised seizures.^[8]

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.^[1]

Further information for healthcare professionals can be found at http://www.eisai.co.uk

About Epilepsy

Epilepsy is one of the most common neurological conditions in the world, affecting approximately one in every one hundred people in Europe, and an estimated 50 million people worldwide.^[9],[10]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 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 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). Zebinix is not approved by Swissmedic.
• 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 Knowledge Centre in Hatfield, UK, Eisai has recently expanded its business operations to include Europe, the Middle East and Africa (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, and the Middle East.

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

References

1. Zhu J et al. Long-term discontinuation rates in an extension study of the AMPA receptor antagonist perampanel as an adjunctive treatment for refractory partial seizures IEC abstract # 1037

2. Simons WR, Gilliam F. Effects of Treatment Response and Side Effects on overall Quality of Life and Distress. IEC abstract # 627

3. Ben-Menachem et al. Long-term seizure outcomes with perampanel in refractory partial-onset seizures and secondarily generalized partial seizures: 10-months additional data from extension study 307 following Phase III clinical trials. IEC abstract # 1330

4. Clément J-F et al. Long-term safety of perampanel: Additional 10 months of data from study 307, an extension of three randomized, placebo-controlled, double-blind, Phase III trials of perampanel in partial-onset seizures in patients aged 12 years and above. IEC abstract # 1161

5. Krauss GL et al. Epilepsia, ePub August 2012

6. Squillacote D et al.  Adjunctive once-daily perampanel reduces seizure frequency and improves responder rates in patients with uncontrolled partial-onset seizures, irrespective of age at epilepsy diagnosis: a pooled analysis of three Phase III trials. IEC abstract #1036

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

8. Fycompa Summary of Product Characteristics. 2012

9. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf [http://www.ibe-epilepsy.org/downloads/EURO Report 160510.pdf ] [Accessed 10 April 2012].

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

Job code: perampanel-UK2129

Date of preparation: June 2013