Eisai is halting its Parkinson's disease late-stage program due to lack of efficacy over placebo. The trials were investigating E2007 (perampanel), which is a highly selective noncompetitive AMPA-type glutamate receptor antagonist with a nondopaminergic mechanism of action. The firm says that it will instead concentrate on advancing this compound in epilepsy and neuropathic pain.
Eisai completed two Phase III evaluations of perampanel as an add-on therapy to levodopa in patients with late-stage disease. The latter trial did not show a significant difference in the primary endpoint of reducing the off time; i.e., the period when signs and symptoms of Parkinson's return as the effect of levodopa wears off.
The company will continue perampanel development in epilepsy and neuropathic pain. The rationale for investigating perampanel in Parkinson's disease was the therapeutic augmentation of levodopa. In neuropathic pain and epilepsy, however, the idea is to direct the compound’s activity as an AMPA receptor antagonist toward inhibition of the neuronal excitability and sensitization caused by glutamate, Eisai explains.
Global Phase III studies with perampanel as add-on therapy in patients with refractory partial seizures are planned to begin soon. Eisai also expects results from a Phase II investigation in painful diabetic neuropathy in September. Another mid-stage study in post-herpetic neuralgia was initiated in January.