First-in-class Fycompa® (perampanel) Demonstrates Improved Seizure Control in Idiopathic Generalised Epilepsy in Two New Sub-analyses of Pivotal Data Presented at the First European Academy of Neurology (EAN) Congress
HATFIELD, England, June 22, 2015 /PRNewswire/ --
PRESS RELEASE FOR EU MEDIA ONLY: NOT FOR AUSTRIAN/SWISS/U.S JOURNALISTS
Important new data for once-daily Fycompa® (perampanel)[1],[2] presented today at the first Congress of the European Academy of Neurology (EAN) in Berlin, Germany. One sub-group analysis shows the effects of adjunctive perampanel on absence and myoclonic seizures in patients with idiopathic generalised epilepsy.[2] A second reports the reduction in primary generalised tonic-clonic (PGTC) seizures observed in the phase III study is independent of age, sex, or race[1].
Perampanel, an oral treatment with a simple titration regimen is currently indicated for the adjunctive treatment of partial-onset seizures with or without secondarily generalised seizures in patients with epilepsy aged 12 years and older.[3] Perampanel received a positive CHMP opinion for the PGTC indication on 27 May 2015 and 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.[4] This mechanism of action is different to other, currently available AEDs.
"For patients with uncontrolled PGTC seizures the treatment armamentarium is limited, perampanel is a first in class treatment with a unique mode of action and good tolerability," comments Bernhard Steinhoff, Medical Director and Executive Chief Physician, Kork Epilepsy Centre, Germany.
Generalised tonic-clonic seizures can be a dangerous type of epilepsy.[5] The seizures start with a loss of consciousness and a sudden contraction of the muscles, which can cause the person to fall down (tonic phase). This is followed by violent convulsions (clonic phase) until the muscles finally relax.[6] Between 20%-40% of people with newly diagnosed epilepsy are, or become refractory to treatment,[7] resulting in a potential negative impact on quality of life.[8]
The sub analyses are part of the first randomised, Phase III, double-blind, placebo-controlled trial to evaluate the efficacy and safety of adjunctive perampanel for the treatment of PGTC seizures in patients aged ≥12 years with idiopathic generalised epilepsy, 164 patients were randomised and included 81 patients who received perampanel and 81 patients who received placebo.[9] Results from Study 332 show the reduction in PGTC seizure frequency was greater in patients receiving perampanel compared with placebo (76.5% vs 38.4%, respectively; P<0.0001).[9] The 50% responder rate for patients with PGTC seizures was also greater with perampanel than placebo (64.2% vs 39.5%, respectively; P=0.0019).[9] Both of these are our primary endpoints. Furthermore, 31% of patients were seizure free during the 13-week maintenance period when treated with perampanel as an adjunctive therapy, compared to 12% in the placebo group.[9] Patients treated with perampanel also experienced improved quality of life across all domains measured, including daily activities, cognition and distress.[9] The adverse event profile in this study were similar to that for other perampanel studies, with the majority of adverse events in both treatment groups being considered mild to moderate in nature - dizziness, fatigue, headache, somnolence and irritability were the most common.[9]
The full analysis set comprised 162 patients (81 placebo; 81 perampanel). 37.0% of patients (n=60) experienced absence seizures and 29.0% (n=47) experienced myoclonic seizures during pre-randomisation. The study was not powered to detect differences in these seizure types, however, there was a numerical reduction in absence seizures with perampanel versus placebo. Myoclonic seizures were reduced in both treatment arms, but the decrease was greater in placebo patients versus perampanel (-52.54% vs -24.47%). Similar proportions of perampanel and placebo patients experienced an increase in myoclonic seizures (30.4% vs 29.2% respectively). Overall, perampanel did not worsen myoclonic seizures. Seizure freedom across all seizures for perampanel versus placebo was 23.5% versus 4.9%.
The development of perampanel demonstrates Eisai's commitment in the therapeutic area of epilepsy and further exemplifies the company's contribution to addressing the diversified needs of and increasing the benefits provided to patients and their families as shown by its human health care (hhc) mission.
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.[3]
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.[8]
For further information please visit: http://www.fycompa.eu
About Phase III study with adjunctive perampanel in idiopathic generalised epilepsy in patients with drug-resistant primary generalised tonic-clonic seizures by age, sex, race[1]
Patients (≥12 years; with IGE confirmed by external Epilepsy Study Consortium review) receiving 1-3 concomitant anti-epileptic drugs for ≥30 days prior to baseline and who had ≥3 PGTCS in the 8 weeks before randomisation were recruited. The study had pre-randomisation (4-week screening, 4-8-week baseline) and randomisation (4-week titration, 13-week maintenance, 4-week follow-up) phases. Perampanel was titrated weekly by 2 mg to 8 mg/day or individual optimal dose. Median percent change from baseline and 50% responder rate were examined by age, sex and race.
162 patients were included in the full analysis set (81 placebo [PBO]; 81 perampanel). The majority of patients were ≥18 years old (n=139), and were White (n=87) or Asian/Pacific (n=68). The proportion of males and females was balanced. Median percent change from baseline in PGTCS frequency was greater with perampanel than placebo (-76.47% vs -38.38%, P<0.0001). Compared with placebo, there were improvements in median percent change from baseline and 50% responder rate across all groups in patients receiving perampanel regardless of age, sex or race. The 50% responder rate was 39.5% for placebo and 64.2% for perampanel.
About Phase III study with adjunctive perampanel in idiopathic generalised epilepsy- subgroup analysis - absence and myoclonic seizures[2]
Patients ≥12 years with ≥3 PGTCS in the 8 weeks before randomisation, receiving 1-3 concomitant anti-epileptic drugs for ≥30 days before baseline were eligible to enrol. The study had pre-randomisation (4-week screening, 4-8-week baseline) and randomisation (4-week titration, 13-week maintenance, 4-week follow-up) phases. Perampanel was increased weekly by 2 mg to 8 mg/day or individual optimal dose. Secondary endpoints included median percent change from baseline and 50% responder rate for absence and myoclonic seizures.
The full analysis set comprised 162 patients (81 placebo; 81 perampanel). 37.0% of patients (n=60) experienced absence seizures and 29.0% (n=47) experienced myoclonic seizures during pre-randomisation. The study was not powered to detect differences in these seizure types, however, there was a numerical reduction in absence seizures with perampanel versus placebo. Myoclonic seizures were reduced in both treatment arms, but the decrease was greater in placebo patients versus perampanel (-52.54% vs -24.47%). Similar proportions of perampanel and placebo patients experienced an increase in myoclonic seizures (30.4% vs 29.2% respectively). Overall, perampanel did not worsen myoclonic seizures. Seizure freedom across all seizures for perampanel versus placebo was 23.5% versus 4.9%.
About Study 332[9]
This Phase III, double-blind, randomised, placebo-controlled, multicentre, parallel-group trial evaluates the efficacy and safety of adjunctive perampanel for refractory tonic-clonic seizures, compared to placebo, amongst 164 patients aged 12 years and older with PGTC seizures receiving one to maximum of three anti-epileptic drugs. The study was conducted across centres in the U.S., Europe, Japan and Asia.
Perampanel was administered via oral tablets, once daily, up to 8 mg/day (titration phase) and then maintained on maximum tolerated dose (maintenance phase). The study period was divided into the pre-randomisation phase (screening and baseline periods): up to 12 weeks, the randomisation phase (treatment): 17 weeks (titration phase, 4 weeks; maintenance phase, 13 weeks) followed by an extension phase.
Results demonstrate that perampanel significantly reduces the number of PGTC seizures (≥50% reduction in seizure frequency per 28 days in the maintenance period, relative to baseline), the study's primary outcome measure, when compared to placebo. Perampanel was generally well tolerated, the most frequent adverse events (10% in the perampanel arm and greater than placebo) were dizziness, fatigue and headache, irritability and somnolence. The adverse event profile in this study is similar to that for other perampanel studies.
About Epilepsy
Epilepsy is one of the most common neurological conditions in the world, affecting approximately 6 million people in Europe, and an estimated 50 million people 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 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
- 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)
- 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). Eisai received a sole license to market, promote and distribute Zebinix® in the following European Countries: Austria, Belgium, Bulgaria, Czech Republic, Belarus, Bosnia, Croatia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Monaco, Netherlands, Norway, Poland, Romania, Russia, Serbia, Slovakia, Slovenia, Spain (co-promotion with Bial from launch) Sweden, Switzerland, Turkey, Ukraine and the United Kingdom
About Eisai Co., Ltd.
Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. 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 our human health care (hhc) philosophy. With over 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realise our hhc philosophy by delivering innovative products in multiple therapeutic areas with high unmet medical needs, including Oncology and Neurology.
As a global pharmaceutical company, our mission extends to patients around the world through our investment and participation in partnership-based initiatives to improve access to medicines in developing and emerging countries.
For more information about Eisai Co., Ltd., please visit http://www.eisai.com.
References
1. Steinhoff B et al. Efficacy of adjunctive perampanel in idiopathic generalised epilepsy patients with drug-resistant primary tonic-clonic seizures by age, sex, race: double-blind PBO-controlled Phase 3 trial. European Academy of Neurology annual meeting 2015; Abstract # 393
2. O'Brien T et al. Efficacy of adjunctive perampanel in idiopathic generalised epilepsy: Subgroup analysis of patients with absence and myoclonic seizures in a double-blind placebo-controlled Phase 3 trial. European Academy of Neurology annual meeting 2015; Abstract # 1362
3. Fycompa, Summary of Product Characteristics (updated September 2014) http://www.medicines.org.uk/emc/medicine/26951/
4. Rogawski M et al. Revisiting AMPA receptors as an antiepileptic drug target. Epilepsy Currents 2011;11:56-63
5. Web MD. Epilepsy Health Centre. http://www.webmd.com/epilepsy/epilepsy-seizure-what-to-do-in-an-emergency Accessed May 2015
6. Epilepsy Action. Generalised seizures. https://www.epilepsy.org.uk/info/seizures/generalised-seizures. Accessed May 2015
7. 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;54:1481-89
8. French J et al. Refractory Epilepsy;Clinical Overview. Epilepsia 2007: 48 (Suppl1) 3-7
9. French J et al. Adjunctive Perampanel RCT for PGTC seizures. Association of British Neurologists annual meeting 2015; Abstract #53141
10. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf (accessed June 2014)
11. Pugliatti M et al. Estimating the cost of epilepsy in Europe: A review with economic modeling. Epilepsia 2007:48(12):2224-33.
Date of preparation: June 2015
Job code: Perampanel-UK2193
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