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    Pooled Phase III Data Supporting Perampanel Partial Epilepsy Treatment
    By News Staff | October 7th 2012 01:00 PM | Print | E-mail | Track Comments

    New data shared today with Europe's epilepsy community at the 10th European Congress on Epileptology (ECE) in London, demonstrated the efficacy of Fycompa(R) (perampanel) in reducing partial-onset seizures, the most common form of epilepsy, and its effectiveness and flexibility of use as add-on therapy. 

    The successful treatment of partial-onset seizures (the most common form of epilepsy) remains a significant challenge in some patients and the incidence of uncontrolled partial epilepsy remains high, despite many existing anti-epileptic drugs (AEDs); between 20 - 40% of patients with epilepsy have remained poorly controlled despite these treatments.[1] The new data supports the use of perampanel as a new therapeutic option for this hard-to-treat patient population.

     Results from two separate analyses of pooled data from the perampanel pivotal Phase III clinical trial program endorse the efficacy and safety of the new AED at clinically relevant doses.[2] In addition, the results show that perampanel decreased the frequency of both complex partial seizures and secondarily generalized seizures.[3] 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.[4] 

     "This first-ever presentation of the pooled data from the perampanel Phase III trial program has been anticipated by the epilepsy community. These results complement to the wealth of efficacy and safety data from the clinical development program supporting the use of the new treatment. In addition, they further demonstrate the important adjunctive role that perampanel may have in the treatment of patients with partial onset seizures in Europe," commented Professor Bernhard Steinhoff Medical Director and Executive at the Epilepsy Centre, Kehl-Kork, Germany. 

    Specific results from the three new analyses include:

    - Abstract 656; E. Ben-Menachem et al.:[2] 1,265 patients (348, 161, 159, 46, 287, 14, 114) patients were included in the safety population for placebo, perampanel 2, 4, 8, 12 mg (randomized dose). Median percent changes in seizure frequency for placebo, 2, 4, 8, 12 mg were -11.7%, -17.3%, -24.1%, -31.9%, -26.2%, respectively. Responder rates were 18.4%, 22.4%, 30.8%, 37.6%, and 39.5%. These data are comparable with randomized results from the individual studies, which did not account for failure to reach assigned doses. Safety analyses were also comparable.

    - Abstract 417; B.J. Steinhoff et al.:[3] 442, 180, 172, 431, and 254 patients were randomised to placebo, perampanel 2, 4, 8, 12 mg, respectively. Median percent changes in CPS+SGS frequency were -14.6% (n=319), -26.6% (n=150), -35.6% (n=145), -35.9% (n=267), -30.3% (n=104) for placebo, perampanel 2, 4, 8, 12 mg actual doses. Responder rates were 21.9%, 29.3%, 37.9%, 40.1%, 39.4%. Median percent changes in SGS frequency were -19.5% (n=133), -27.9% (n=60), -54.6% (n=66), -60.8% (n=112), -56.0% (n=43) for placebo, 2, 4, 8, 12 mg. Responder rates were 38.3%, 43.3%, 53.0%, 56.3%, 53.5%

    - Abstract 669; E. Trinka et al.:[4] Median changes from baseline in seizure frequency for the five most common concomitant AEDs in the pooled perampanel Phase III studies are provided for placebo, 4, 8, 12 mg, respectively. Carbamazepine: -13% (n=128), -24% (n=49), -30% (n=116), -18% (n=65); valproate: -18% (n=128), -28% (n=69), -31% (n=94), -26% (n=31); lamotrigine: -13% (n=112), -25% (n=64), -33% (n=113), -37% (n=36); levetiracetam: -18% (n=116), -19% (n=46), -31% (n=92), -39% (n=46); oxcarbazepine: -5% (n=80), -36% (n=24), -32% (n=54), -38% (n=21). 50% responder rates for each of the AEDs were generally consistent with the median percent changes.

    Discovered and developed by Eisai in Europe and Japan, perampanel is the first and only licensed AED in Europe with a mode of action that selectively targets AMPA receptors, which are thought to play a central role in seizure generation and spread.[5] This first in class treatment selectively targets the transmission of seizures by blocking the effects of glutamate, which can trigger and maintain seizures. In addition, perampanel has the added benefit of convenient, once-daily dosing taken at bedtime,[6] and it is the only contemporary epilepsy treatment approved for adolescents from launch which can lead to earlier seizure control in younger patients.

     The European Commission's (EC) Marketing Authorisation Approval of perampanel was based on three global pivotal Phase III studies with 1,480 subjects. These randomized, double-blind, placebo-controlled, and dose-escalated studies showed consistent results in the efficacy and tolerability of perampanel as an adjunctive therapy in patients with partial-onset seizures (with or without secondary generalizations).[7],[8],[9] The most commonly reported adverse events were dizziness, headache, somnolence, irritability, fatigue, falls, and ataxia.[7],[8],[9] 

    The development of perampanel underscores Eisai's human health care 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 committed to the therapeutic area of epilepsy and addressing the unmet medical needs of patients and their families.

    References

    1. French JA. Refractory Epilepsy; Clinical Overview. Epilepsia 2007: 48 (Suppl1) 3 - 7

    2. Ben-Menachem E,Krauss GL, Noachtar S et al. Abstract presented at ECE 2012

    3. Steinhoff BJ, Gauffin H, McKee P et al. Abstract presented at ECE 2012

    4. Trinka E, Straub H, Squillacote D et al. Abstract presented at ECE 2012

    5. Rogawski MA. Epilepsy Currents 2011;11:56-63

    6. Fycompa Summary of Product Characteristics. 2012

    7. Krauss GM. Serratosa JM, Villanueva V et al. Neurology 2012: Available at: http://www.neurology.org/ .

    8. French JA. Neurology 2012;79:589-596.

    9. French J, et al. 2011, IEC Rome. Abstract# 122/ Ref 020.

    10. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf [Accessed 10 April 2012].

    11. Pugliatti M, et al. Epilepsia 2007: 48(12) 2224 - 2233.