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. 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 programme endorse the efficacy and safety of the new AED at clinically relevant doses. In addition, the results show that perampanel decreased the frequency of both complex partial seizures and secondarily generalised seizures. 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.
"This first-ever presentation of the pooled data from the perampanel Phase III trial programme has been anticipated by the epilepsy community. These results complement to the wealth of efficacy and safety data from the clinical development programme 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.: 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.: 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.: 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.
The European Commission's (EC) Marketing Authorisation Approval of perampanel was based on three global pivotal Phase III studies with 1,480 subjects. These randomised, double-blind, placebo-controlled, and dose-escalated studies showed consistent results in the efficacyand tolerability of perampanel as an adjunctive therapy in patients with partial-onset seizures (with or without secondary generalisations).,, The most commonly reported adverse events were dizziness, headache, somnolence, irritability, fatigue, falls, and ataxia.,,
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.