HATFIELD, England, April 15, 2016 /PRNewswire/ --

Poster and abstract presentation times:  

Sunday 17 April 08:30 - 17:30 PDT: P2.021, P2.024, P2.045, P2.044, P2.056, P2.043
Wednesday 20 April 08:30 - 19:00 PDT: Poster: P5.405

PRESS RELEASE FOR EU MEDIA ONLY: NOT FOR AUSTRIAN/SWISS/US JOURNALISTS 

Other Phase III data for perampanel in partial seizures show long-term adjunctive treatment improves seizure control with good tolerability 

Sub-group analysis of Phase III data show that Inovelon^® (rufinamide) demonstrates significant seizure reduction in adults with Lennox-Gastaut Syndrome 

Data show that seizure control improves regardless of age, sex and ethnicity in drug-resistant patients with primary generalised tonic-clonic (PGTC) seizures treated with once-daily adjunctive Fycompa^® (perampanel) at doses up to 8mg per day.^[1] These data are one of a number of perampanel and Inovelon^® (rufinamide) abstracts presented this week at the American Academy of Neurology (AAN) Annual Meeting Vancouver, Canada.

The results show that a change in seizure frequency from baseline is greater with perampanel than with placebo across all groups and similar for placebo between age, sex, and ethnicity. Data are obtained from a double-blind, placebo-controlled Phase III study in 162 patients with idiopathic generalised epilepsy (IGE) (81 each on either perampanel or placebo)^[1] who have confirmed PGTC seizures.

"These data confirm that adjunctive perampanel provides effective management of seizures in all groups of IGE patients studied with primary generalised tonic-clonic seizures," comments Bernhard Steinhoff, Medical Director and Executive Chief Physician, Kork Epilepsy Centre, Germany.

Post-hoc analysis of this Phase III study of adjunctive perampanel for primary tonic-clonic seizures across age, sex and ethnicity shows similar median percent change from baseline in primary generalised tonic-clonic seizure frequency for age (age <18y, 88.0%; age ≥18−<65y, 74.4%), sex (males, 53.3%; females, 83.0%) and ethnic groups (White, 65.5%; Asian/Pacific, 79.1%). The 50% responder rate is also similar across age (age <18y, 53.8%; age ≥18<65y, 66.2%), sex (males, 54.3%; females, 71.7%), and ethnic groups (White, 68.2%; Asian/Pacific, 58.8%).

Perampanel 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 seizures in adult and adolescent patients from 12 years of age with idiopathic generalised epilepsy.^[2]  

Abstract P2.024 17 April 08:30-17:30 PDT Krauss et al^[3]

Data presented from this Phase III study in PGTC seizures explores the relationship between perampanel exposure, primary generalised tonic-clonic seizure outcomes, and treatment-emergent adverse events (TEAEs) in patients with uncontrolled primary generalised tonic-clonic seizures.^[3] Response rate increases, and responder probability is predicted to increase with increased perampanel exposure. Concomitant use of enzyme-inducing anti-epileptic drugs (EIAED) reduces perampanel exposure, and perampanel exposure is higher in patients with hostility/aggression-related TEAEs than in those without, although the concentrations overlap substantially.^[3]

Abstract P2.045 17 April 08:30-17:30 PDT French J et al^[4]

Data from an external review was used for the first time to ensure the appropriate classification of trial participants^[4] with primary generalised tonic-clonic seizures in the Phase III perampanel PGTC trial. An independent group review eliminated almost a third (29.9%) of patients, initially considered eligible, from inclusion in perampanel's pivotal study 332.^[5] Without this review the interpretability of results may otherwise be compromised.^[4]  

Abstract P2.044 17 April 08:30-17:30 PDT Tsong et al^[6]

With the advent of newer medications for primary generalised tonic-clonic seizures the standard of care (SOC) has changed over time while trial designs remain similar over time, according to a systematic literature review of published data during 19892014 of different anti-epileptic drug (AED) trials versus placebo for adjunctive treatment of primary generalised tonic-clonic seizures.^[6] The latest trial, the perampanel Phase III study 332^[5] includes a standard of care that is weighted to the most recently approved drugs for primary generalised tonic-clonic seizures such as topiramate, lamotrigine, levetiracetam, and valproate.^[5]

Abstract P5.405 20 April 08:30-19:00 PDT Perucca et al^[7]

In patients with partial seizures, results of an extension study show that treatment with perampanel for three or four years significantly improves seizure control, and is well tolerated as an adjunctive treatment.^[7] At three years' exposure to perampanel, median seizure reduction is 61.98% and at four years' exposure is 70.63%. The largest median percent decrease during the last year of treatment occurs in patients with secondarily generalised seizures at baseline - at three years, seizure reduction is 87.96% and at four years is 100%.^[7]

"We are proud to share these data on the use of perampanel to manage partial-onset seizures and primary generalised tonic-clonic seizures, both seizure types with life-limiting outcomes where treatment with perampanel can make a real difference, Eisai is committed to the exploration of effective treatments for people affected by epilepsy," comments Neil West, Vice President, Global Neurology Business Unit, Eisai EMEA.

Abstract P2.056 17 April 08:30-17:30 PDT Striano et al^[8] Abstract P2.043 17 April 08:30-17:30 PDT Ng et al^[9]

A sub-group analysis of another Phase III trial shows that rufinamide demonstrates favourable efficacy as adjunctive treatment for adults with Lennox-Gastaut syndrome^[8] (LGS), a severe and rare form of childhood-onset epilepsy, which affects nearly 208,000 people in Europe.^[10] Median change from baseline in seizure frequency was -31.5% for rufinamide (n=21) versus +22.1% for placebo (n=21), this represents a statistically significant difference in favour of rufinamide (p=0.008).

Further data reported at AAN 2016^[9] in 138 people with LGS aged 4-37, shows no evidence of tolerance to rufinamide during short-term and long-term treatment. Larger median decreases in both total and tonic-atonic seizure frequency for rufinamide versus placebo are evident as early as two weeks and over the course of treatment for rufinamide (total: -20.6%−-43.1%; tonic-atonic: -22.8%−-50.3%) than for placebo (total: 1.3%−-1.5%; tonic-atonic: -1.3%−1.0%), which suggests a fast onset of action and lack of short-term tolerance to rufinamide.

Rufinamide efficacy continues up to three years. Over the course of open-label treatment from 336 months, progressive median decreases in seizure frequency for total seizures are 31.6% to 79.3% and for tonic-atonic seizures are 41.9% to 76.1%.^[9]

Rufinamide is currently indicated for adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in children four years and older.^[11] Effective Lennox-Gastaut Syndrome management and compliance to treatment is of key importance to patients, as the condition is characterised by a high number of seizures - up to 70 seizures a day. The condition often persists into adulthood and most people with this condition will have developmental delay, mental retardation, and moderate to severe learning disabilities, in addition to physiological and behavioural problems.^[12],[13]

The development of perampanel and rufinamide demonstrates Eisai's commitment to 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 mission.

Notes to Editors  

About Fycompa^® (perampanel)  

Perampanel 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.

Perampanel 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 seizures in adult and adolescent patients from 12 years of age with idiopathic generalised epilepsy.^[2]

Since launch, perampanel has helped treat 39,588 people living with epilepsy across Europe.^[14]

About Inovelon^® (rufinamide)  

Rufinamide was approved for adjunctive therapy for Lennox-Gastaut Syndrome in Europe (under the brand name Inovelon) in 2007.^[11] Inovelon is available in 19 European countries as film-coated tablets containing 100mg, 200mg, and 400mg rufinamide. It is available in some countries as an oral suspension in orange flavour 40mg/ml concentration. The oral suspension formulation is bioequivalent to the tablet formulation on a milligram per milligram basis and is available in Denmark, France, Germany, Portugal, Spain, and the United Kingdom.

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).^[14]

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

• Fycompa^® (perampanel) Perampanel is indicated for use as a once-daily, adjunctive therapy for both primary generalised tonic-clonic seizures with idiopathic generalised epilepsy and for adjunctive treatment of partial onset seizures, with or without secondary generalised seizures, in patients with epilepsy aged 12 years or older
• Inovelon^® (rufinamide) for the adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in patients >4 years. (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 six years and above. (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)

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 Generalized Epilepsy Patients with Drug-Resistant Primary Generalised Tonic-Clonic Seizures by Age, Sex, and Race: Double-Blind Placebo-Controlled Phase III Study. P2.021; AAN 2016 

2. Fycompa, Summary of Product Characteristics. Available at: http://www.medicines.org.uk/emc/medicine/26951/ (Accessed March 2016) 

3. Krauss G, et al. Relationship between Perampanel Exposure, Seizure Outcomes and Treatment-Emergent Adverse Events (TEAEs) in Patients with Primary Generalised Tonic-Clonic Seizures (PGTCS): a Randomised, Double-Blind (DB) Phase III Study. P2.024; AAN 2016 

4. French J, et al. Secondary Screening of Patients in Randomised Perampanel Primary Generalised Tonic-Clonic Seizures (PGTCS) Study Excludes 29.9% of Eligible Patients Due to Inaccurate Classification. P2.045; AAN 2016 

5. French A, et al. Perampanel for Tonic-Clonic Seizures in Idiopathic Generalised Epilepsy. Neurology 2015;85:950-57 

6. Tsong W, et al. Systematic Literature Review of Adjunctive Anti-Epileptic Drug Trials in Patients with Primary Generalised Tonic-Clonic Seizures Illustrates Changes in Standard of Care Over 12-20 Years. P2.044; AAN 2016 

7. Perucca E, et al. Marked Reduction in Secondarily Generalised Seizures (SGS) in Patients Treated With Perampanel for 3 and 4 Years. P5.405; AAN 2016 

8. Striano P, et al. Efficacy of Rufinamide as Adjunctive Treatment for Adults with Lennox-Gastaut Syndrome: Subgroup Analysis from a Phase III Trial. P2.056; AAN 2016 

9. Ng Y, et al. Response Durability Analyses from a Rufinamide Pivotal Trial in Lennox-Gastaut Syndrome (LGS). P2.043; AAN 2016 

10. Rare Diseases.Org. Available at: https://rarediseases.org/rare-diseases/lennox-gastaut-syndrome/ (Accessed March 2016) 

11. Inovelon tablets Summary of Product Characteristics Available at: http://www.medicines.org.uk/emc/medicine/20165/SPC/ (Accessed March 2016) 

12. International Journal of Pharma and Bio Sciences. Available at: http://www.ijpbs.net/issue-3/82.pdf (Accessed March 2016) 

13. MedScape references Lennox-Gastaut Syndrome. Available at: http://emedicine.medscape.com/article/1176735-overview (Accessed March 2016) 

14. Eisai Data on File, 2015 

Date of preparation: April 2016
Job code: Perampanel-UK2196

SOURCE Eisai