2.2 Dementia-Related Psychosis

Pimavanserin – Dementia-Related Psychosis


Innovation

Pimavanserin is a proprietary small molecule currently being researched and developed for dementia-related psychosis. Pimavanserin is a selective serotonin inverse agonist (SSIA) preferentially targeting 5-HT2A receptors that are thought to play an important role in dementia-related psychosis.

About Dementia-Related Psychosis

Around 8 million people in the United States are living with dementia and studies suggest that approximately 30% of dementia patients, or 2.4 million people have psychosis, commonly consisting of delusions and hallucinations.

Dementia-related psychosis includes psychosis in:
–  Alzheimer’s disease
–  Dementia with Lewy bodies
–  Parkinson’s disease dementia
–  Vascular dementia
–  Frontotemporal dementia

Serious consequences have been associated with severe or persistent psychosis in patients with dementia, such as repeated hospital admissions, increased likelihood of nursing home placement, progression of dementia, and increased risk of morbidity and mortality. No drug is approved by the FDA for the treatment of dementia-related psychosis.

Status

The Phase 3 HARMONY study, a randomized, double-blind, placebo-controlled relapse prevention study evaluating the efficacy and safety of pimavanserin for the treatment of delusions and hallucinations associated with dementia-related psychosis has met the study’s primary endpoint at the planned interim efficacy analysis, with pimavanserin demonstrating a highly statistically significant longer time to relapse of psychosis compared to placebo. As a result, we are stopping the study for efficacy and will bring in patients for final visits, conduct safety follow-up, and proceed with the full analysis of the study data.

The HARMONY study included a broad population of patients with the most common subtypes of dementia including: Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease dementia, vascular dementia, and frontotemporal dementia spectrum disorders. During the 12-week open-label stabilization period patients with dementia-related psychosis were treated with pimavanserin 34 mg once daily. Dose reduction to 20 mg once daily was allowed if clinically justified within the first four weeks. Following the 12-week stabilization period, patients who met pre-specified criteria for treatment response were then randomized into the double-blind period of the study to continue their pimavanserin dose (34 mg or 20 mg per day) or switched to placebo and followed for up to 26 weeks or until a relapse of psychosis occurred. The primary endpoint in the study was time to relapse in the double-blind period.

The FDA previously granted Breakthrough Therapy Designation for pimavanserin for the treatment of dementia-related psychosis.

Important Note:

Information presented above is related to an investigational use of pimavanserin. Pimavanserin is not approved by the FDA for the treatment of delusions and hallucinations associated with dementia-related psychosis. Please see below FDA approved indication for pimavanserin, including Important Safety Information & Boxed WARNING.

Important Safety Information and Indication for NUPLAZID (pimavanserin)

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS  

    • Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
    • NUPLAZID is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson’s disease psychosis.
  • Contraindication: NUPLAZID is contraindicated in patients with a history of a hypersensitivity reaction to pimavanserin or any of its components. Rash, urticaria, and reactions consistent with angioedema (e.g., tongue swelling, circumoral edema, throat tightness, and dyspnea) have been reported.
     
  • QT Interval Prolongation: NUPLAZID prolongs the QT interval.
    • The use of NUPLAZID should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong QT interval including Class 1A antiarrhythmics or Class 3 antiarrhythmics, certain antipsychotic medications, and certain antibiotics.
    • NUPLAZID should also be avoided in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and presence of congenital prolongation of the QT interval.
  • Adverse Reactions: The most common adverse reactions (≥2% for NUPLAZID and greater than placebo) were peripheral edema (7% vs 2%), nausea (7% vs 4%), confusional state (6% vs 3%), hallucination (5% vs 3%), constipation (4% vs 3%), and gait disturbance (2% vs <1%).
     
  • Drug Interactions:
    • Coadministration with strong CYP3A4 inhibitors (e.g., ketoconazole) increases NUPLAZID exposure. Reduce NUPLAZID dose to 10 mg taken orally as one tablet once daily.
    • Coadministration with strong or moderate CYP3A4 inducers reduces NUPLAZID exposure. Avoid concomitant use of strong or moderate CYP3A4 inducers with NUPLAZID.

Indication: NUPLAZID is indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis.

Dosage and Administration: Recommended dose: 34 mg capsule taken orally once daily, without titration.

NUPLAZID is available as 34 mg capsules and 10 mg tablets.

Please see full Prescribing Information including Boxed WARNING for NUPLAZID.