Pimavanserin treatment of hallucinations and delusions in patients with Parkinson’s disease dementia: post hoc analysis of the HARMONY trial (P1-1.Virtual)

Objective: Describe the efficacy and safety of pimavanserin 34 mg for the treatment of hallucinations and delusions in a subgroup of patients with Parkinson’s Disease dementia (PDD) in HARMONY.

Background: Pimavanserin 34 mg is approved in the US to treat hallucinations and delusions associated with Parkinson’s Disease psychosis (PDP) and was investigated for the treatment of dementia-related psychosis (DRP), including PDD patients, in HARMONY.

Design/Methods: HARMONY (NCT03325556) was a Phase 3, placebo-controlled, randomized discontinuation study. Eligible patients received pimavanserin for 12 weeks during the open-label (OL) period (N=392). Patients with sustained response at weeks 8 and 12 were randomized 1:1 to continue pimavanserin or receive placebo for up to 26 weeks in the double-blind (DB) period. The primary endpoint was time from randomization to psychosis relapse. The Extrapyramidal Symptom Rating Scale-Abbreviated (ESRS-A) and Mini-Mental State Examination (MMSE) were used to evaluate motor function and cognition.

Results: 59 enrollees had PDD and initiated pimavanserin 34 mg, 49/59 continued to receive pimavanserin 34 mg. In the OL period, most PDD patients (73.5% [36/49]) exhibited a sustained response and were randomized to pimavanserin (n=16) or placebo (n=20). The risk of psychosis relapse was lower with pimavanserin than placebo (hazard ratio: 0.052; 95% CI: 0.016, 0.166; 1-sided P<0.0001). 1 pimavanserin-treated and 9 placebo-treated patients met relapse criteria. In the OL period, 46.9% (n=23) of patients experienced any treatment-emergent adverse event (TEAE). During the DB period, TEAE rates were balanced (pimavanserin, 31.3% [n=5], placebo, 45.0% [n=9]). There was no negative effect of pimavanserin on ESRS-A or MMSE scores over the duration of the study.

Conclusions: Pimavanserin 34 mg reduced the risk of psychosis relapse in PDD patients. Pimavanserin was well tolerated, with no negative effect on motor or cognitive function. These data show the maintenance of antipsychotic efficacy and safety of pimavanserin in PDD patients.

Disclosure: Daniel Weintraub has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Clintrex. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Scion. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Signant. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sunovion. Daniel Weintraub has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Movement Disorder Society. The institution of Daniel Weintraub has received research support from NIH. The institution of Daniel Weintraub has received research support from Fox Foundation. The institution of Daniel Weintraub has received research support from IPMDS. Daniel Weintraub has received intellectual property interests from a discovery or technology relating to health care. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neuroderm. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amneal. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadia. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acorda. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyowa Kirin. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sunovion. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bexion. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Supernus (formerly USWorldMeds). Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadia. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AskBio. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Supernus (formerly, USWorldMeds). Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sunovion. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Acadia. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amneal. The institution of Dr. Espay has received research support from NIH. The institution of Dr. Espay has received research support from Michael J Fox Foundation for Parkinson's Research. Dr. Espay has received intellectual property interests from a discovery or technology relating to health care. Dr. Espay has received publishing royalties from a publication relating to health care. Dr. Espay has received publishing royalties from a publication relating to health care. Dr. Espay has received publishing royalties from a publication relating to health care. Dr. Sharma has nothing to disclose. Pierre Tariot has received personal compensation for serving as an employee of Banner Alzheimer's Institute. Pierre Tariot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbvie. Pierre Tariot has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AC Immune. Pierre Tariot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Axsome. Pierre Tariot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for WebMD. Pierre Tariot has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arcadia. Pierre Tariot has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Pierre Tariot has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BioXcel. Pierre Tariot has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cortexyme. Pierre Tariot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Pierre Tariot has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for eNOVA. Pierre Tariot has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Pierre Tariot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Syneos. Pierre Tariot has received intellectual property interests from a discovery or technology relating to health care. Dr. Abler has received stock or an ownership interest from Acadia Pharmaceuticals . Dr. Pathak has received personal compensation for serving as an employee of Acadia Pharmaceuticals. Srdjan Stankovic has received personal compensation for serving as an employee of ACADIA Pharmaceuticals, Inc.. Srdjan Stankovic has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Neurogene Inc.. Srdjan Stankovic has stock in ACADIA Pharmaceuticals, Inc.. Srdjan Stankovic has stock in Neurogene, Inc..