New Data for Fycompa® (Perampanel) Demonstrate Improved Seizure Response and Control Rates in Two Types of Epilepsy

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21 May, 2015, 23:01 GMT

HATFIELD, England, May 22, 2015 /PRNewswire/ --

PRESS RELEASE FOR EU MEDIA ONLY: NOT FOR SWISS/AUSTRIAN/U.S JOURNALISTS 

Data to be presented at the Association of British Neurologists Annual Meeting 2015 show potential of perampanel in hard to treat epilepsy  

New data from two Eisai supported studies demonstrate the efficacy and safety of once-daily anti-epilepsy treatment Fycompa® (perampanel) in the adjunctive treatment of people with partial onset seizures (POS) and primary generalised tonic-clonic (PGTC) seizures.[1],[2] These studies will be presented at the prestigious annual meeting of the Association of British Neurologists, Harrogate, United Kingdom, 20-22 May 2015.

Interim analyses of a multi-centre, retrospective, one-year, observational FYDATA study (abstract no. 53144) in a real-life setting for people (n=111) with highly refractory POS demonstrated that nearly one in 10 (9%) of those on a mean dose of 5.4mg perampanel achieved seizure freedom and a ≥50% reduction in seizures was observed in 44%.[1] Perampanel was found to be well tolerated at the three month analyses and adverse events were consistent with those previously reported for perampanel and include irritability (14%), somnolence (11%) and dizziness (10%).

Perampanel is licensed for the adjunctive treatment of partial onset seizures, with or without secondarily generalised seizures, in patients with epilepsy aged 12 years and older 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.[3],[8] This mechanism of action is different to other currently available AEDs. In addition, perampanel has the added benefit of convenient, once-daily dosing at bedtime and, significantly, is the only new-generation partial epilepsy treatment approved to treat adolescents with epilepsy from launch.[8]

"These data based on real-life experience of patients and doctors in the clinic underscore the important role that new treatment options such as perampanel continue to play in the management of epilepsy and seizure control. It is encouraging that the real-world data in focal (partial onset) seizures show benefits that are even greater than those observed in clinical trials," comments Professor Eugen Trinka, Professor and Chair of the Department of Neurology, Paracelsus Medical University, Salzburg, Austria. "This study reflects what I see in clinical practice and is the reason why I commonly use perampanel as the first adjunct treatment for those with focal (partial onset) seizures. Effective management of epilepsy allows people to continue everyday activities without the concern of seizures."

For the first time in Europe, a second study presented at the meeting entitled 'Adjunctive Perampanel RCT for PGTC seizures' by J French et al (abstract no. 53141), assessed the efficacy and safety of perampanel for PGTC seizures in people 12 years or older (n=164).[2]  Results from this randomised study show that the 50% PGTC seizure responder rate was significantly improved (P=0.0019) for patients receiving perampanel (64%) versus placebo (40%). Significantly, during the 13-week maintenance phase of the study almost a third (31%) of those randomised to perampanel were free of PGTC seizures versus only 12% for patients randomised to placebo. Perampanel treatment was well tolerated and the most common adverse events were consistent with the known profile of perampanel.

"The data from these two studies confirm Eisai's commitment to address the medical needs of people with epilepsy and their families. We will continue to support research into our portfolio to ensure that people with different types of epilepsy is fulfilled," comments Mike Bee, Epilepsy Business Unit Director, Eisai EMEA.

The continued development of perampanel underscores Eisai's human health care (hhc) mission, the company's commitment to innovative solutions in disease prevention, cure and care for the health and well-being of people worldwide. Eisai is proud to market more epilepsy products in EMEA than any other company.

Notes to Editors 

About Perampanel 

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.

Further information can be found at http://www.fycompa.eu  

About the Perampanel Pooled Data (Study 306, 305 and 304)[4],[5],[6] 

The pooled Phase III data analysed the efficacy of once-daily perampanel in reducing partial onset seizures, the most common form of epilepsy, and its effectiveness and flexibility of use as add-on therapy. Efficacy end points 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), 306 (n=386) and 306 (n=705).

Median reductions in partial seizure frequency were greater with perampanel 4 mg (-23.3%), 8 mg (-28.8%), and 12 mg (-27.2%) than placebo (-12.8%; p<0.01, each dose vs placebo). Median (95% CI) differences from placebo in changes in partial seizure frequency were -12.2% (-20.1 to -4.6), -17.9% (-24.1 to -11.8), and -15.8% (-23.0 to -8.7) for perampanel 4, 8, and 12 mg, respectively.[7]

50% responder rates were greater with perampanel 4 mg (28.5%), 8 mg (35.3%), and 12 mg (35.0%) than placebo (19.3%; p<0.05, each dose vs placebo). Median reductions in complex partial seizure frequency were greater with perampanel 4 mg (-31.2%), 8 mg (-35.6%), and 12 mg (-28.6%) than placebo (-13.9%).[8]

Results from two separate analyses of pooled data from the perampanel pivotal Phase III clinical trial programme endorse the efficacy and safety of the new AED at clinically relevant doses.[8] In addition, the results show that perampanel decreased the frequency of both complex partial seizures and secondarily generalised seizures.[9] In a third analysis of the pooled trial data, patients with uncontrolled partial onset seizures taking any of the five most commonly-used AEDs with perampanel as an add-on therapy experienced a reduction in their seizure frequency. Patients generally received additional benefit from increased doses of perampanel.[10]

Perampanel was generally well tolerated; most adverse events were mild/moderate.

About the FYDATA study- Perampanel Study in a Real-Life Setting[1]

FYDATA is a multi-centre, retrospective, 1-year, observational study (inclusion criteria: written informed consent to review clinical charts; patients ≥12 years old; partial-onset seizure [POS] diagnosis; perampanel treatment according to clinical practice as add-on therapy; patients with ≥1 POS in year prior to starting perampanel). The source of data was patient clinical records collected by physicians.

An interim analysis was performed at 3 months in 111 patients (mean age: 37.8 years; mean epilepsy duration: 24 years). Mean seizure number/month at onset was 19.3. At baseline, patients had tried a mean of 8.3 antiepileptic drugs (AEDs) and half were taking ≥3 concomitant AEDs. 31% of patients had a comorbid psychiatric condition.

About the adjunctive perampanel randomised control trial for primary generalised tonic clonic (PGTC) seizures study[2]

Efficacy and safety of perampanel (selective noncompetitive AMPA receptor antagonist) for primary generalised tonic-clonic (PGTC) seizures were assessed.

164 patients 12 years and above were randomized; full analysis set included 81 patients each on perampanel and placebo. Median percent change in PGTC seizure frequency/28 days during Titration/ Maintenance versus Baseline was -76.5% with perampanel versus -38.4% placebo; P<0.0001. 50% PGTC seizure responder rate was 64.2% with perampanel versus 39.5% placebo; P=0.0019. During Maintenance, 30.9% of perampanel patients were free of PGTC seizures versus 12.3% placebo. Treatment-emergent AEs (TEAEs) occurred in 82.7% of perampanel and 72.0% placebo patients; most common dizziness, fatigue, headache, somnolence, irritability. Serious TEAEs occurred in 6 (7.4%) perampanel and 7 (8.5%) placebo patients (one death in the perampanel group [accidental drowning; not treatment-related], one with placebo).

Adjunctive perampanel treatment up to 8mg improved seizure control in PGTC seizure patients, with almost a third free of PGTC seizures during Maintenance. Perampanel was well tolerated.

About Primary Generalised Tonic-Clonic Seizures 

Generalised tonic-clonic seizures are one of the most dangerous types of seizure. For the majority of patients, a primary generalised tonic-clonic (PGTC) seizure begins with a loss of consciousness without any prior warning symptoms and a sudden contraction of the tonic muscles, causing the patient to fall down (tonic phase). This is followed by violent convulsions (clonic phase) until the muscles finally relax, and the patient is left with a disturbance of consciousness. 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.[11]

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.[12],[13] 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:

  • 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
  • Inovelon® (rufinamide) for the adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in patients >4 years. (Rufinamide was originally developed by Novartis)
  • Zebinix® (eslicarbazepine acetate) as adjunctive therapy in adult patients with partial onset seizures, with or without secondary generalisation. (Zebinix is under license from BIAL)
  • Zonegran® (zonisamide) as monotherapy in adults and adjunctive therapy in adults, adolescents and children aged six years and above with partial onset seizures, with or without secondary generalisation. (Zonegran is under license from the originator Dainippon Sumitomo Pharma)

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. Villanueva V et al. Fydata study: retrospective analysis of adjunctive perampanel in a real-life setting. Association of British Neurologists annual meeting 2015; Abstract #53144
  2. French J et al. Adjunctive Perampanel RCT for PGTC seizures. Association of British Neurologists annual meeting 2015; Abstract #53141
  3. Rogawski MA. Revisiting AMPA receptors as an antiepileptic drug target. Epilepsy Currents 2011;11:56-63
  4. Krauss GM. et al. Randomized phase III study 306: Adjunctive perampanel for refractory partial-onset seizures. Neurology 2012;78:1408-1415
  5. French JA. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology 2012;79:589-596
  6. 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;54:117-25
  7. Ben-Menachem E et al. Abstract presented at ECE 2012
  8. Fycompa, Summary of Product Characteristics (updated September 2014): http://www.medicines.org.uk/emc/medicine/26951/
  9. Steinhoff BJ, Gauffin H, McKee P et al. Abstract presented at ECE 2012
  10. Trinka E et al. Abstract presented at ECE 2012
  11. Epilepsy Foundation. Types of seizures. Available at: http://www.epilepsy.com/learn/types-seizures. Last Accessed May 2015
  12. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf (Accessed April 2015)
  13. 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: May 2015
Job code: Perampanel-UK2188