Eisai Announces Change in Regulatory Submission Strategy of E2007 for Parkinson's Disease

Eisai Co., Ltd. (Headquarters: Tokyo, President & CEO: Haruo Naito) announced today that the Company has decided to change the regulatory submission timing of E2007 (generic name: perampanel), which is under clinical investigation worldwide aiming to be the first oral AMPA receptor antagonist available for conditions including Parkinson's disease, neuropathic pain, epilepsy, migraine prophylaxis and multiple sclerosis. Eisai originally planned to file E2007 for approval in the U.S. and Europe for Parkinson's disease as the first indication within fiscal year 2007 but will do so in the fourth quarter of fiscal year 2008.

E2007, a new chemical entity developed by Eisai, has the novel mechanism of action of selectively antagonizing AMPA-type glutamate receptors. It is believed to show promise in the treatment of various neurologic diseases because AMPA receptors are widely distributed in nerves.

Eisai is conducting three Phase Ⅲ studies (Studies 301, 302 and 309), primarily in the U.S. and Europe, for Parkinson's disease. The 30-week Study 301, which compared E2007 to placebo as an add-on therapy to levodopa for patients who have idiopathic Parkinson's disease, has been completed and analysis of its results is ongoing.

According to the currently available analysis results, E2007, compared with placebo, did not show a significant difference in the primary endpoint of reduction in “off” time (time when Parkinson's symptoms return as the effect of levodopa wears off). However, the study did show that E2007 was well tolerated and no significant safety issues were observed.

Preclinical study results demonstrated that E2007 prolonged both levodopa's duration of action and the time Parkinsonian symptoms were improved while improving the dyskinesia caused by levodopa. Additionally, the results of Study 204, Phase Ⅱ POC (proof of concept) study, showed that E2007 reduced the “off” time in a significant dose-related manner. These results indicate that E2007 shows promise in the treatment of Parkinson's disease by prolonging levodopa's duration of action.

Eisai has decided to proceed with detailed analyses of Study 301 results (e.g. dose of levodopa, effects of concomitant drugs, etc.) and utilize the findings in planning the analyses to be performed for currently ongoing Studies 302 and 309 to clarify the efficacy and safety of E2007. Eisai plans to complete Studies 301, 302 and 309 under this policy and submit applications for E2007 in the U.S. and Europe in the fourth quarter of fiscal year 2008.

Concurrently, other clinical trials to investigate the efficacy and safety of E2007 for various indications, including neuropathic pain and epilepsy, are ongoing. Eisai plans to submit the E2007 application for neuropathic pain in fiscal year 2010, following the submission for Parkinson's disease.

Eisai remains committed to treating patients with cerebral and neurologic diseases and to increasing their quality of life through development of various new pharmaceuticals in addition to E2007.

Glutamic acid is a common neurotransmitter used in central neuronal cells. It is known that excessive stimulation by glutamic acid causes excessive inflow of calcium ions into cells, resulting in central nerve cell death. AMPA receptors, one type of three ion-channel-type glutamate receptors, are believed to be engaged in almost all neuronal transmissions at excitatory synapses.

E2007 selectively antagonizes AMPA receptors and inhibits neuronal cell death. This mechanism was studied mainly by researchers at Eisai's London Research Laboratories and published in the UK's ppeer reviewed journal “Nature Medicine”. (L. Steinman, Nature Medicine 6(1) 15-16, 2000)

1) Effects of E2007 on preclinical Parkinson's model
In a study designed to compare effects of E2007 and levodopa in MPTP (1-Methyl 4- phenyl 1,2,3,6-tetrahydropyridine), E2007 did not affect levodopa's maximum effect on Parkinson's disease symptoms, however, it significantly both prolonged levodopa's effective time and improved the severity of dyskinesia.
Presented at International Congress of Parkinson's Disease and Movement Disorders on November 2, 2006

2) Effects of E2007 on rotational behavior of levodopa
E2007 prolonged levodopa's duration of action in a preclinical study for 6OHDA-hemi-parkinsonian model.
Presented at International Congress of Parkinson's Disease and Movement Disorders on November 2, 2006.