Pimavanserin alone or in combination for use in the treatment of Alzheimer's disease psychosis

Inventors

Coate, Bruce DuaneOwen, James RandallKnowles, Mark DonaldStankovic, Srdjan R.Youakim, James M.

Assignees

Acadia Pharmaceuticals Inc

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Publication Number

US-11464768-B2

Patent

Publication Date

2022-10-11

Expiration Date


Abstract

Methods for the treatment of Alzheimer's disease psychosis, or a symptom thereof, comprising administering pimavanserin. Also provided herein are methods for the treatment of delusions and/or hallucinations in a human with dementia comprising administering pimavanserin, or a pharmaceutically acceptable salt thereof. Also provided herein are methods for reducing NPI-NH score in a human with Alzheimer's Disease comprising administering pimavanserin, or a pharmaceutically acceptable salt thereof. Also provided herein are methods for reducing agitated behavior or aggressive behavior in a human with dementia comprising administering pimavanserin, or a pharmaceutically acceptable salt thereof.

Core Innovation

The invention describes methods using pimavanserin to treat delusions and/or hallucinations in a human with dementia. The method comprises orally administering 34 mg pimavanserin to the human and selecting the human based on baseline NPI-NH scores, including a baseline score of 12 or greater in the Psychosis subscale (Domains A and B) and/or a baseline score of 6 or greater in the Agitation/Aggression subscale (Domain C).

The invention defines treatment effect by an improved patient score in the NPI-NH of at least 4 points as compared to the baseline score prior to administering pimavanserin. The clinical evaluation includes the psychosis Domains A and B, the agitation Domain C, and additional related NPI-NH subscales such as sleep/nighttime (Domain K), with instruments and endpoints including CMAI, CMAI-SF, ADCS-CGIC, and ADCS-ADL.

The invention includes a clinical trial example using a randomized, double-blind, placebo-controlled design with pimavanserin administered at 34 mg daily, and reports statistically significant NPI-NH psychosis improvements in specified baseline subgroups. Salt and formulation aspects are included, including pimavanserin tartrate, and the invention describes optional contexts involving anti-Alzheimer’s agents.

Claims Coverage

The claim set covers a treatment method using orally administered 34 mg pimavanserin for delusions and/or hallucinations in a human with dementia, with patient selection based on specific NPI-NH baseline thresholds and treatment response defined by at least a 4-point NPI-NH improvement versus baseline. Dependent claims add timing, statistical, formulation, and co-therapy refinements.

Oral administration of 34 mg pimavanserin for delusions and/or hallucinations in dementia

A method for the treatment of delusions and/or hallucinations in a human with dementia, comprising orally administering 34 mg of pimavanserin to the human.

NPI-NH baseline thresholds for eligibility

The human has a baseline score of 12 or greater in the Psychosis subscale (Domains A and B) of the NPI-NH; or has a baseline score of 6 or greater in the Agitation/Aggression subscale (Domain C) of the NPI-NH.

NPI-NH improvement of at least 4 points versus baseline

The effect of the treatment is determined by an improved patient score in the NPI-NH of at least 4 points as compared to baseline score prior to administering pimavanserin.

Assessment of improvement after about 6 weeks

The effect is determined by an improved patient score at least about 6 weeks after initial administration of pimavanserin.

Statistical criterion for improvement p-value range

The improvement has a p-value between 0.0001 and 0.05.

Use of pimavanserin tartrate

The method involves administering a tartrate salt of pimavanserin to a human.

Concomitant administration with an anti-Alzheimer's agent

Pimavanserin is administered during concomitant administration of an anti-Alzheimer's agent.

Overall, the claim set covers a dementia treatment method using oral 34 mg pimavanserin for delusions and/or hallucinations, with selection by NPI-NH Psychosis and/or Agitation/Aggression thresholds and response defined by at least a 4-point NPI-NH improvement versus baseline. Dependent claims further specify timing, statistical p-value range, pimavanserin tartrate, and concomitant administration with an anti-Alzheimer’s agent.

Stated Advantages

Statistically significant NPI-NH psychosis improvements in specified baseline subgroups.

Reported safety and tolerability, including no cognitive impairment reported in the provided summary.

Documented Applications

Treatment of delusions and/or hallucinations in a human with dementia, including selection based on NPI-NH psychosis and/or agitation/aggression subscale baseline thresholds.

Clinical evaluation using NPI-NH, including psychosis domains, agitation domain, and sleep/nighttime domain, and additional instruments/endpoints CMAI, CMAI-SF, ADCS-CGIC, and ADCS-ADL.

Optionally used in a context involving concomitant administration of an anti-Alzheimer’s agent.

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