Real World Data to be Presented for Fycompa® (perampanel) at the European Congress on Epileptology (ECE) 2014

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Eisai Europe Limited

29 Jun, 2014, 23:01 GMT

HATFIELD, England, June 30, 2014 /PRNewswire/ --

Further analyses of pivotal Phase III data for perampanel will also be presented for first time at ECE 

Real world data for Fycompa® (perampanel) have been published in 10 abstracts in Epilepsia and will be presented for the first time this week at the XXI European Congress on Epileptology (ECE) in Stockholm, Sweden. In addition, subset data from the Phase III pivotal trials of perampanel will be unveiled at the congress. Perampanel is indicated for the adjunctive treatment of partial onset seizures, with or without secondarily generalised seizures, in patients with epilepsy aged 12 years and older.[1]

The 10 Eisai-supported observational studies evaluate real world experience with adjunctive perampanel in over 350 refractory patients across sites in the UK and Austria.[2-11] The data show perampanel as well tolerated in a variety of patient populations, including those with highly refractory epilepsy and those with a high number of comorbidities.

In two further abstracts, metabolic parameters were assessed for the perampanel pooled Phase III global pivotal studies (n=1,480)[12] and an open-label extension study (n=1,186).[13] Results show that lipid parameters (blood cholesterol and triglyceride levels) and glucose levels remain stable over time across a range of doses (up to 12mg per day) of perampanel. The most common metabolic treatment emergent adverse event reported for both studies was weight increase.[12],[13]

A study that assessed the impact of perampanel on behaviour in adolescents with refractory partial onset seizures (12-17 years old, n=133) is the subject of an additional abstract at ECE.[14]

"Data such as these add to the growing weight of evidence that supports the use of perampanel for adults and adolescents with refractory epilepsy. Treatments, such as perampanel are an important adjunctive therapy option," commented Sten Friberg, Nordic Medical Director for Eisai Europe.

Perampanel is the only licensed anti-epileptic drug (AED) to selectively target AMPA receptors, a protein in the brain which plays a critical role in the spread of seizures.[15] Perampanel has the added benefit of convenient, once-daily dosing at bedtime[1] and, significantly, is the only new-generation partial onset epilepsy treatment approved to treat adolescents (>12 years) from launch.

The data presented at ECE underscore Eisai's human health care (hhc) mission; the company's commitment to provide innovative solutions in disease prevention, cure and care for the health and wellbeing of people worldwide. Eisai is proud to currently market more epilepsy products in EMEA than any other company.

Notes to Editors 

About Fycompa® (perampanel) 

Perampanel is indicated for the adjunctive treatment of partial onset seizures, with or without secondarily generalised seizures, in patients with epilepsy aged 12 years and older.[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[16] 

The main objective of the pooled analysis of the results of the three Phase III studies (304[17], 305[18] and 306[19]) was to compare the efficacy and tolerability of perampanel, administered in one daily dosage with that of the placebo in combination therapy in patients aged 12 and above with partial seizures uncontrolled by one to three AEDs. The primary efficacy endpoint of the three studies for EU registration was the rate of responders (defined as the percentage of patients achieving a reduction in the frequency of all partial onset seizures by at least 50% for a period of 28 days of treatment).  

The data from each efficacy end point 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), 305 (n=386) and 306 (n=705).

The results of the pooled analysis showed that median reductions in partial seizure frequency were greater with perampanel 4mg (-23·3%), 8 mg (-28·8%), and 12mg (-27·2%) than placebo (-12·8%; p<0·01, each dose vs. placebo). 50% responder rates were greater with perampanel 4mg (28·5%), 8mg (35·3%), and 12mg (35·0%) than placebo (19·3%; p<0·05, each dose vs. placebo). Median reductions in complex partial and secondary generalized seizure frequency were greater with perampanel 4mg (-31·2%), 8mg (-35·6%), and 12mg (-28·6%) than placebo (-13·9%). Perampanel was generally well tolerated with most adverse events being mild or moderate.

About Study 307[20] 

The Phase III open-label extension study (n=1,218) of patients from pivotal trials 304[17], 305[18], 306[19] was designed to evaluate safety, tolerability, and seizure outcome data during long-term treatment with once-daily adjunctive perampanel in people with refractory partial onset seizures.

Patients aged ≥12 years with partial-onset seizures despite treatment with one to three antiepileptic drugs at baseline completed a perampanel Phase III trial and entered extension study 307 (NCT00735397). Patients were titrated to 12mg/day (or their individual maximum tolerated dose) during the blinded conversion period, followed by open-label maintenance. Exposure, safety (adverse events, vital signs, weight, electrocardiography [ECG], laboratory values) and seizure outcomes were analysed; key measures were assessed by geographic regions.

Results show that after titration/conversion, responder rate and median percentage change from baseline in seizure frequency were stable for perampanel: 46% for both measures at nine months (in 980 patients with ≥9 months' exposure) and 58% and 60%, respectively, at two years (in the 337 patients with 2 years' exposure).In patients with at least two years perampanel exposure and secondary generalised seizures at baseline (n=141), an up to 90% reduction in secondary generalised seizures was observed. Among the 694 patients with maintenance data for at least one year, 5.3% were seizure-free for the entire year.

The study showed that among 1,216 patients perampanel was well tolerated up to 3.3 years at a median daily dose of 10.6 mg/day. The most frequent adverse events reported in ≥10% of patients were dizziness, somnolence, headache, fatigue, irritability and weight increase. Only dizziness and irritability caused discontinuation from the study in >1% of patients (3.9% and 1.3%, respectively).

Safety and seizure responses were similar across a large number of geographical regions and ethnicities (249 centres in 39 countries), with high treatment retention at the study end (average 58.5%).

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.[21],[22] 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:

  • Fycompa® (perampanel) for the adjunctive treatment for partial onset seizures, with or without secondarily generalised seizures, in patients with epilepsy aged 12 years and older
  • Zonegran® (zonisamide) as monotherapy in the treatment of partial seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy and as adjunctive therapy in the treatment of partial seizures, with or without secondary generalisation, in adults, adolescents, and children aged 6 years and above (Zonegran is under license from the originator Dainippon Sumitomo Pharma)
  • Zebinix® (eslicarbazepine acetate) as adjunctive therapy in adults with partial onset seizures, with or without secondary generalisation (Zebinix is under license from BIAL)
  • Inovelon® (rufinamide) for the adjunctive therapy in the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients four years of age and older (Rufinamide was originally developed by Novartis)

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 management
  • 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

References 

  1. Fycompa, Summary of Product Characteristics (updated November 2013): http://www.medicines.org.uk/emc/medicine/26951/ [http://www.medicines.org.uk/emc/medicine/26951 ]  
  2. Philip S et al. Efficacy and tolerance of perampanel in pharmacoresistant epilepsy in children and young people. Abstract presented at ECE 2014. P126   
  3. Sieradzan K et al. Efficacy and tolerability of perampanel in patients with refractory partial epilepsy in a tertiary epilepsy centre. Abstract presented at ECE 2014. P137   
  4. Parrett M et al. A service evaluation of perampanel in Cornwall. Abstract presented at ECE 2014. P334     
  5. Flynn C et al. Seizure response to perampanel in a severe refractory group of epilepsy patients. Abstract presented at ECE 2014. P343     
  6. Manidakis I et al. Perampanel in the treatment of epilepsy; a multicentre evaluation. Abstract presented at ECE 2014. P562     
  7. Geldard J et al. A service evaluation of perampanel (Fycompa) at Leeds General Infirmary. Abstract presented at ECE 2014. P335     
  8. Coyle H et al. Clinical experience with perampanel in a regional epilepsy clinic. Abstract presented at ECE 2014. P563     
  9. Lawthom C et al. Perampanel in South Wales: A multi-centre clinical evaluation. Abstract presented at ECE 2014. P138     
  10. Kelly K et al. Adjunctive perampanel in highly drug-resistant localization-related epilepsy - a prospective audit. Abstract presented at ECE 2014. P119     
  11. Baumgartner C et al. First clinical experiences with perampanel in Vienna. Abstract presented at ECE 2014. P573  
  12. Brodie MJ et al. Evaluation of metabolic parameters over time in the perampanel pooled Phase III epilepsy studies. Abstract presented at ECE 2014. 009    
  13. Patsalos PN et al. Effects of perampanel on metabolic parameters in patients with refractory partial-onset seizures in extension study 307. Abstract presented at ECE 2014. 010
  14. Lagae L et al. Impact of adjunctive perampanel on behaviour in adolescents with refractory partial-onset seizures. Abstract presented at ECE 2014. P558    
  15. Rogawski MA. Revisiting AMPA receptors as an antiepileptic drug target. Epilepsy Currents 2011:11:56-63
  16. Steinhoff B et al. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three Phase III studies. Epilepsia 2013:54(8):1481-9
  17. French JA et al. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304.Neurology 2012:79(6):589-596
  18. French JA et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: Results of randomized global phase III study 305. Epilepsia 2013:54(1):117-125
  19. Krauss GM et al. Randomized phase III study 306: Adjunctive perampanel for refractory partial-onset seizures. Neurology 2012:78(18):1408-1415
  20. Krauss GL et al. Long-term safety of perampanel and seizure outcomes in refractory partial-onset seizures and secondarily generalised seizures: Results from Phase III extension study 307. Epilepsia 2014; DOI: 10.1111/epi.12643 (available at http://onlinelibrary.wiley.com/doi/10.1111/epi.12643/pdf)
  21. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf (Accessed June 2014)
  22. Pugliatti M et al. Estimating the cost of epilepsy in Europe: A review with economic modeling. Epilepsia 2007:48(12):2224-2233.

Date of preparation: June 2014
Job code: perampanel-UK2160