First-in-class Epilepsy Treatment Fycompa® (perampanel) Has New Indication For Primary Generalised Tonic-Clonic Seizures in Idiopathic Generalised Epilepsy

MELBOURNE, Australia, September 14, 2016 /PRNewswire/ --

PRESS RELEASE FOR AUSTRALIAN MEDICAL MEDIA ONLY   

Anti-epileptic treatment now available in Australia for people affected by primary generalised tonic-clonic seizures associated with idiopathic generalised epilepsy  

Fycompa^®, a once-daily epilepsy treatment, is now available in Australia for adjunctive treatment of primary generalised tonic-clonic (PGTC) seizures in adults and adolescents (≥12 years) with idiopathic generalised epilepsy (IGE).^[1] Fycompa is the first and only licensed anti-epileptic drug to selectively, non-competitively target AMPA receptors, a type of receptor that can play a critical role in the generation and spread of seizures.^[1],[2] Few antiepileptic drugs are licensed to treat PGTC seizures.^[3]

Fycompa was first made available in Australia in 2014 for the adjunctive treatment of partial-onset seizures, with or without secondarily generalised seizures, in patients with epilepsy aged 12 years and older.^[1] Since launch, approximately 52,000 people living with epilepsy across the EMEA region^[a] have been treated with Fycompa.^[4]

There are approximately 225,000 people in Australia with epilepsy^[5] and it is estimated that idiopathic generalised epilepsy make up 20 per cent of all epilepsies, with PGTC seizures being the most common seizure type.^[6] The number of anti-epileptic drugs licensed for the treatment of PGTC seizures is limited and as many as 20 per cent of people with idiopathic generalised epilepsy remain uncontrolled despite treatment.^[3],[6]

PGTC 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 seizures (clonic phase) until the muscles finally relax.^[7] There is a risk of injury with PGTC seizures, including bone fractures and burns^[8] and they can have long-term consequences.^[9] The frequency of generalised tonic-clonic seizures increases the risk of Sudden Unexpected Death in Epilepsy (SUDEP).^[10]

"This new indication for Fycompa is a welcome advance for people living with idiopathic generalised epilepsy who experience tonic-clonic seizures. This serious seizure type has a potential high risk for injury or even death for people with epilepsy," comments John Bower, Market Access and Medical Director of Eisai Australia.

In study 332, a pivotal Phase III randomised, double-blind, placebo-controlled study, 164 patients age 12 years or older taking 1-3 anti-epileptic drugs with PGTC seizures and IGE were randomised to receive adjunctive Fycompa (8mg/d or highest tolerated dose) or placebo in a 1:1 ratio (4-week titration period and 13 week maintenance period).^[11] Fycompa subjects achieved a greater 50% PGTC seizure responder rate (≥50% reduction in PGTC seizure frequency; maintenance versus baseline) compared with placebo (64.2% vs 39.5%, respectively; P=0.0019).^[11] Fycompa showed a greater median per cent reduction in PGTC seizure frequency per 28 days compared with placebo (76.5% vs 38.4%; P<0.0001).^[11]Furthermore, 31% of patients were PGTC seizure free during the 13-week maintenance period when treated with Fycompa as an adjunctive therapy, compared to 12% in the placebo group (P-value not reported).^[11]

The adverse event profile in study 332 in people with PGTC seizures was similar to that observed for the controlled Phase III studies in people with partial onset seizures.^[1],[11] The most common treatment-emergent adverse events with Fycompa (≥10%) were dizziness, fatigue, headache, somnolence and irritability.^[1],[11]

"Approval for our first-in-class treatment Fycompa in the PGTC indication is a positive step, building on the medicine's availability in focal seizures. Importantly, it also evidences Eisai's human health care mission, including our commitment to epilepsy and to improving outcomes for the many Australians living with this disease, and their families," states Jaime McCoy, Country POA, Sales & Marketing Director, Eisai, Australia.

Minimum Product Information: Fycompa® (perampanel). INDICATIONS: Adjunctive treatment of partial-onset seizures with or without secondarily generalised seizures in adult and adolescent patients from 12 years of age with epilepsy. Adjunctive treatment of primary generalised tonic-clonic seizures in adult and adolescent patients from 12 years of age with idiopathic generalised epilepsy. CONTRAINDICATIONS: Hypersensitivity to perampanel or any of the excipients.PRECAUTIONS: Not recommended in children <12 years; use in elderly (use with caution); suicidal ideation and behaviour (monitor for emergence or worsening depression, suicidal thoughts or behaviour and unusual changes in mood or behaviour); nervous system disorders (dizziness, gait disturbance, somnolence and fatigue); falls (caution with elderly); recommend gradual discontinuation; serious psychiatric and behavioural reactions (monitor for changes in mood, behaviour or personality, particularly during titration and higher doses. Reduce dose if symptoms occur, discontinue if severe); abuse potential (caution with history of substance abuse); monotherapy not recommended; galactose intolerance (do not take with galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption); pregnancy (category B3), not recommended; unknown if excreted in human milk (assess risk benefit). INTERACTIONS: Oral contraceptives (consider decreased efficacy of progestative containing OCs for women needing 12mg/day and additional non-hormonal form of contraception); other antiepileptic drugs (AEDs; enzyme inducers carbamazepine, phenytoin, oxcarbazepine and topiramate) increase perampanel clearance and decrease concentration,  dose to clinical effect regardless of other AEDs; dose of perampanel may need to be adjusted according to CYP450 inhibitor and inducer coadministration; possible additive effects with CNS depressants (alcohol). ADVERSE REACTIONS : Dizziness, somnolence, fatigue, irritability, falls, nausea, ataxia, balance disorder, gait disturbance, back pain, vertigo, headache and weight gain. DOSAGE AND ADMINISTRATION: Film-coated tablets: 2 mg, 4 mg, 6 mg, 8 mg, 10 mg and 12 mg.  Adults and adolescents: Initiate at 2 mg and titrate weekly or longer according to individual response to maintenance dose of 4 mg/day to 12 mg/day. Take orally once daily at bedtime, with or without food, swallowed whole with a glass of water. Not recommended in moderate or severe renal impairment or patients undergoing haemodialysis.  Caution in mild to moderate hepatic impairment, do not exceed 8 mg.  Not recommended in severe hepatitic impairment.  Date of most recent amendment: 12 May 2016.  

PBS Information: Authority required (STREAMLINED). Intractable partial epileptic seizures. Refer to PBS Schedule for full authority information.

Please review the Product Information before prescribing, available from www.eisai.com.au/PI 

Fycompa^® is a registered trademark of Eisai Australia Pty Ltd, PO Box 33004, Melbourne VIC 3004. ABN 73 117 970 993. Eisai Australia Medical Information: 03-9832-9100 or medinfo_australia@eisai.net.

Notes to Editors  

About Fycompa^®    

Fycompa is a highly selective, non-competitive AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptor antagonist. 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.^[2]

Fycompa has shown efficacy in, and is indicated for the adjunctive treatment of partial-onset seizures with or without secondarily generalised seizures in adult and adolescent patients from 12 years of age with epilepsy; and for the adjunctive treatment of primary generalised tonic-clonic (PGTC) seizures in adult and adolescent patients from 12 years of age with idiopathic generalised epilepsy.^[1]

Further information for healthcare professionals can be found at www.eisai.com.au   

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.^[12] It is a collection of syndromes that have many possible causes but often the cause is unknown. 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 seizures. 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.^[13]

For the majority of idiopathic generalised epilepsy patients, a primary generalised tonic-clonic (PGTC) seizure begins with or without an aura (sensory or psychic phenomena), which is followed by loss of consciousness and muscle rigidity (tonic phase). This is followed by violent muscle contractions (clonic phase). As this is a serious event, it is seen as a major hindrance on daily life. While the seizure generally only lasts a few minutes, the patient will often feel confused or drowsy for a short period of time before returning to normal.^[7] PGTC seizures can also result in risk of injury^[8] and sudden unexpected death in epilepsy (SUDEP).^[10]

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 Australia, Eisai currently has one marketed product for the treatment of epilepsy:

• Fycompa^® is indicated for use as a once-daily, adjunctive therapy for both primary generalised tonic-clonic seizures with idiopathic generalised epilepsy and for partial onset seizures, with or without secondarily generalised seizures, in patients with epilepsy aged 12 years or older

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.

a. EMEA countries are Germany, Italy, UK, Spain, France, Switzerland, Netherlands, Ireland, Sweden, Norway, Denmark, Austria, Belgium, Czech Republic, Portugal, Greece, Australia, Russia, Slovakia

References  

1. Approved Fycompa® Product Information. Available at: http://www.eisai.com.au/media/1778/1312-product-information-clean-australia.pdf

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

3. Rheims S and Ryvlin P. Pharmacotherapy for tonic-clonic seizures. Exp Opin Pharmacother 2014;15:1417-26

4. Eisai. Data on File 2016 - PER211

5. Epilepsy Action Australia. Facts and statistics about Epilepsy. Available at: http://www.epilepsy.org.au/resources/for-media/facts-statistics-about-epilepsy. Accessed September 2016

6. Curatolo P, et al. Pharmacotherapy of idiopathic generalised epilepsies. Expert Opinion on Pharmacotherapy 2009; Jan;10(1):5-17. doi: 10.1517/14656560802618647 

7. Epilepsy Foundation. Types of seizures. Available at: http://www.epilepsy.com/learn/types-seizures/tonic-clonic-seizures. Accessed September 2016

8. Asadi-Pooya A, et al. Physical injuries in patients with epilepsy and their associated risk factors. Seizure 2012;21:165-68

9. Trinka E, et al. A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia 2015;56(10):1515-23

10. SUDEP Action. What is SUDEP? Available at: https://sudep.org/what-sudep-1. Accessed September 2016

11. French J, et al. Perampanel for tonic-clonic seizures in idiopathic generalised epilepsy. Neurology 2015;85 (11):950-57

12. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf. Accessed September 2016

13. World Health Organisation - Epilepsy fact sheet (updated February 2016) Available at: http://www.who.int/mediacentre/factsheets/fs999/en/. Accessed September 2016

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