Pimavanserin - a potential first line therapy for Parkinson's disease psychosis

Abstract

Pimavanserin (ACP-103) is a novel and selective 5-HT_2A inverse agonist currently in Phase III development for Parkinson’s disease psychosis (PDP).  Most antipsychotic drugs cannot be used for this indication because their prominent dopamine receptor blocking potency counteracts the dopamine replacement therapy used to alleviate the motor symptoms of Parkinson’s disease (PD).  There is currently no first line therapy approved for PDP in the EU or the USA despite the well established unmet medical need for this indication which afflicts up to 40% of PD patients.

 

In addition to demonstrating activity in a variety of established animal models of schizophrenia (JPET, 317, 910-918, 2006), we have now shown that pimavanserin, in contrast to currently marketed antipsychotics, potentially normalizes deficits in prepulse inhibition and augmented behavioral responses to amphetamine in rodent models of PDP while not counteracting L-DOPA induced turning in unilaterally lesioned rodents.  These data, which indicate that pimavanserin can be differentiated from current antipsychotic off-label therapy for PDP by providing antipsychotic activity, while allowing for optimal motor control, are further supported by a proof-of-concept Phase II study which demonstrated that doses of pimavanserin that do not worsen motor symptoms of PD provide a clinically meaningful reduction in psychosis in patients with PDP as measured by the SAPS.

 

ACADIA Pharmaceuticals Inc., San Diego, USA