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NUPLAZID® (pimavanserin) logo - once daily - 34 mg capsules NUPLAZID® (pimavanserin) logo - once daily - 34 mg capsules

NUPLAZID® (pimavanserin) is indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease (PD) psychosis.

Real-World Evidence

Retrospective Analyses Comparing All-Cause Mortality Risk Associated With Atypical Antipsychotics Used to Treat PD Psychosis

Multiple retrospective analyses have been conducted among Medicare beneficiaries with PD or PD psychosis (100% sample) to evaluate the risk of all-cause mortality associated with NUPLAZID vs off-label atypical antipsychotics. See below for study details and key findings.

Important Safety Information
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 who experience psychosis unless their hallucinations and delusions are related to Parkinson’s disease.
Mortality findings from placebo-controlled studies
  • In the NUPLAZID 6-week, placebo-controlled, clinical studies at approval, 3 (1.5%) deaths were reported among patients with PD psychosis treated with NUPLAZID 34 mg (N=202) vs 1 (0.4%) death in a patient treated with placebo (N=231)1
Important considerations

  • Information from these retrospective analyses has not been reviewed by the FDA and is not meant to rebut the current risk information, including the Boxed WARNING, for NUPLAZID or other APs as described in each product’s FDA‐approved labeling

  • This section does not include findings from all retrospective analyses evaluating the comparative risk of all-cause mortality associated with NUPLAZID vs off-label atypical APs in patients with PD psychosis

  • Two retrospective analyses presented here are based on the following considerations: a data source appropriate for capturing patients with PD psychosis and for measuring mortality as an endpoint; large, comprehensive studies with broad representation of the treatment population; and sound study methodology and statistical approach, including appropriate patient selection criteria and matching/weighting to address potential confounding

  • NUPLAZID is the only FDA‐approved treatment for hallucinations and delusions associated with PD psychosis. By providing this information, Acadia Pharmaceuticals Inc. is not recommending or suggesting that an off‐label use of other atypical APs for the treatment of PD psychosis is appropriate

The following key limitations of retrospective analyses should be considered when interpreting the authors’ findings:

  • Definitive conclusions regarding any differences or lack thereof in mortality rates between or among APs, including NUPLAZID, should not be drawn based on these findings

  • Direct causation between a drug and reported mortality rates in patients with PD cannot be established, which includes not only the risk of mortality but also, conversely, any impact on overall survival of the patient population

  • The potential exists for selection bias, unknown prognostic factors, underreporting of adverse events, and residual confounding

  • Heterogeneity in characteristics of NUPLAZID users may have arisen over the study period. Heterogeneity may also have been present in indications for atypical APs, which have been used off‐label for insomnia or agitation

Mosholder et al Study

Retrospective Analysis Comparing All-Cause Mortality Risk Associated With Atypical APs Used to Treat PD Psychosis2

The objective of the Mosholder study was to evaluate all-cause mortality risk in patients with PD treated with NUPLAZID compared with off-label atypical APs.* The study utilized data from Medicare beneficiaries enrolled in Parts A, B, and D from April 2016 to March 2019.

Study details2

Table shows select study details of the Mosholder study
Table shows select study details of the Mosholder study

Probability of survival among patients with PD taking NUPLAZID or off-label atypical APs (weighted cohort)2

Graph shows all-cause mortality risk for up to 360 days of follow-up for NUPLAZID® vs off-label atypical antipsychotics
Graph shows all-cause mortality risk for up to 360 days of follow-up for NUPLAZID® vs off-label atypical antipsychotics

Note: A statistical evaluation showed that the proportional hazard assumption was violated in this analysis. The authors subsequently performed 2 separate piecewise time-interval analyses for days 1-180 and days 181+. These segmented analyses satisfied the proportional hazard assumption.2

All-cause mortality outcomes among patients with PD, overall and in 2 separate piecewise analyses2

Chart shows hazard ratio of all-cause mortality risk overall and by time interval for NUPLAZID® vs off-label atypical antipsychotics
Chart shows hazard ratio of all-cause mortality risk overall and by time interval for NUPLAZID® vs off-label atypical antipsychotics
  • First time-interval analysis (1-180 days): 35% lower mortality risk among patients treated with NUPLAZID vs off-label atypical APs*
  • Second time-interval analysis (180+ days): No additional mortality advantage was seen with NUPLAZID
  • Above findings are limited to patients in the community setting (85% of the study population). Nursing home residents were 15% of the population. In this subgroup, the HR was 1.05 (95% Cl, 0.73-1.52) for days 1 through 180 and 1.54 (95% Cl, 0.91-2.63) for days over 181

Select sensitivity analyses2

Table shows select sensitivity analyses findings from the publication
Table shows select sensitivity analyses findings from the publication
  • Before weighting, 78% (n= 14,463) of the atypical APs cohort were taking quetiapine. 79% of that cohort were taking quetiapine ≤50 mg
  • Additional sensitivity analyses included: 2-prescriptions analysis; NUPLAZID 34 mg dose analysis; neurologist visit within 90 days; death or hospice admission outcome; censoring for entry to SNF; 30-day gap allowance; time -varying QT-prolonging drug analysis; unweighted unadjusted Cox; unweighted covariate-adjusted Cox; and unweighted lasso covariate-adjusted Cox. The results were consistent with those of the main analysis. See publication for additional details.

*Quetiapine, risperidone, olanzapine, and aripiprazole.

AP=antipsychotics; Cl=confidence interval; HR=hazard ratio; SNF=skilled nursing facility.

Important considerations:

  • The findings from the retrospective analyses presented here are descriptive and should be interpreted with caution as the studies were not designed or powered to make direct safety comparisons between APs, and due to high patient attrition over time. The data are not intended to show an independent treatment effect of product on survival
  • Due to study design differences, cross-study comparisons should not be made
  • Please see additional important considerations and also review the publication for other study limitations

Retrospective Analysis Comparing All-Cause Mortality Risk Associated With Atypical APs Used to Treat PD Psychosis3

The primary objective of the Layton study was to compare all-cause mortality risk in patients with PD psychosis initiating NUPLAZID vs those initiating off-label atypical APs.* The secondary objective was to evaluate whether mortality risk varies over time or in subgroups, including long-term care and skilled nursing facilities. The study was conducted by researchers at RTI Health Solutions. Data came from Medicare beneficiaries enrolled in Parts A, B, and D, and Minimum Data Set (MDS) 3.0 assessments from April 2016 to December 2019.

Study details3

Table shows select study details of the Layton study
Table shows select study details of the Layton study

Cumulative incidence of mortality since atypical AP initiation in patients with PD psychosis (matched cohort)3

Chart shows overall cumulative all-cause mortality risk in patients treated with NUPLAZID® vs off-label atypical antipsychotics
Chart shows overall cumulative all-cause mortality risk in patients treated with NUPLAZID® vs off-label atypical antipsychotics

All-cause mortality among patients with PD psychosis, overall and by follow-up period3

Chart shows hazard ratio of all-cause mortality risk for primary cohort and subcohort, overall and by follow-up period, for NUPLAZID® vs off-label atypical antipsychotics
Chart shows hazard ratio of all-cause mortality risk for primary cohort and subcohort, overall and by follow-up period, for NUPLAZID® vs off-label atypical antipsychotics

In the primary PD psychosis cohort after propensity score matching:

  • For the first 180 days of treatment, cumulative mortality risk was 34% lower in patients treated with NUPLAZID vs off-label atypical APs*
  • Cumulative mortality risk at 1 year was 23% lower in patients treated with NUPLAZID vs off-label atypical APs3*

In the matched cohort, ~86% of patients were taking quetiapine.

*Clozapine, quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole.

APs=antipsychotics; Cl=confidence interval; HR= hazard ratio; LTC= long-term care; MDS=Minimal Data Set; SNF=skilled nursing facility.

Important considerations:

  • The findings from the retrospective analyses presented here are descriptive and should be interpreted with caution as the studies were not designed or powered to make direct safety comparisons between APs, and due to high patient attrition over time. The data are not intended to show an independent treatment effect of product on survival
  • Due to study design differences, cross-study comparisons should not be made
  • Please see additional important considerations and also review the publication for other study limitations

Learn more about the safety of NUPLAZID

Go to safety data

Explore the proven efficacy of NUPLAZID

View efficacy data
Proposed MOA
Expert Perspectives

IMPORTANT SAFETY INFORMATION and INDICATION

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 who experience psychosis unless their hallucinations and delusions are related to Parkinson’s disease.
  • 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.

  • Warnings and Precautions: 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 (e.g., Class 1A antiarrhythmics, Class 3 antiarrhythmics, certain antipsychotics or 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 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 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, with or without food.

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

Please read the full Prescribing Information, including Boxed WARNING.

References:
  1. Acadia Pharmaceuticals Inc. NUPLAZID Advisory Committee Briefing Document. San Diego, CA: Sponsor Background Information for a Meeting of the Psychopharmacologic Drugs Advisory Committee. March 29, 2016.
  2. Mosholder AD, Ma Y, Akhtar S, et al. Mortality among Parkinson’s disease patients treated with pimavanserin or atypical antipsychotics: an observational study in Medicare beneficiaries. Am J Psychiatry. 2022;179(8):553-561.
  3. Layton JB, Forns J, McQuay LJ, et al. Mortality in patients with Parkinson’s disease-related psychosis treated with pimavanserin compared with other atypical antipsychotics: a cohort study. Drug Safety. Published online December 14, 2022. doi:10.1007/s40264-022-01260-6.
  4. Layton JB, Forns J, McQuay LJ, et al. Mortality in patients with Parkinson’s disease-related psychosis treated with pimavanserin compared with other atypical antipsychotics: a cohort study. Supplementary material. Online resource. Drug Safety. Published online December 14, 2022. doi:10.1007/s40264-022-01260-6.

Safety & Tolerability