CLINICAL TRIALS PROFILE FOR NUPLAZID

All Clinical Trials for NUPLAZID

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT03947216 ↗	Randomized Placebo Controlled Trial Evaluating the Efficacy of Pimavanserin, a Selective Serotonin 5-HydroxyTryptamine-2A (5HT2A) Inverse Agonist, to Treat Impulse Control Disorders in Parkinson's Disease.	Recruiting	EUCLID Clinical Trial Platform	Phase 2	2020-10-23	There is no consensus on the treatment of Impulse Control Disorder (ICD) in Parkinson Disease (PD) though it is recommended to reduce the dosage of dopamine agonists (DA). Reduction of DA frequently leads to a worsening of motor signs (parkinsonism or dyskinesias due to the concomitant increase of levodopa doses) and non-motor signs with the appearance of a DA withdrawal syndrome (DAWS). Chronic stimulation of the sub-thalamic nuclei may reduce ICD but is restricted to a minority of patients and cases of new-onset ICD symptoms post stimulation have been reported. The benefit of amantadine in pathological gambling is controversial and the efficacy of clozapine has been reported in a few cases but with serious safety limitations. Very recently, naltrexone did not significantly improve ICD. Thus, an efficacious and safe treatment of ICD in PD remains an unmet need for clinical practice. Recently, it has been reported that pimavanserin, a selective serotonin 5-HT2A inverse agonist with a satisfactory safety profile without motor side effects, was efficient in improving psychosis, insomnia and day-time sleep in PD. Pimavanserin, marketed under the tradename NUPLAZID® was approved in 2016 by the U.S. Food and Drug Administration (FDA) for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. The link between serotonin and ICD has been well established, since the enhancement of 5HT2A receptors stimulation is associated to ICD, since serotonin modulates mesolimbic dopaminergic reward system transmission and given that serotonin neurotransmission is increased during chronic intake of dopamine agonist such as pramipexole which is well-known to induce ICD in PD patients. Thus, there is a large body of evidence suggesting that the decrease of the 5HT2A activity could be efficient in reducing ICD in PD. This further supports the concept of testing the efficacy of pimavanserin (a selective 5HT2A inverse agonist) for treating ICD in PD. Our aim is to conduct a study evaluating the efficacy and safety of pimavanserin on ICD in PD. This clinical trial is conducted with the support of the French NS-Park/FCRIN (French Clinical Research Infrastructure Network) network.
NCT03947216 ↗	Randomized Placebo Controlled Trial Evaluating the Efficacy of Pimavanserin, a Selective Serotonin 5-HydroxyTryptamine-2A (5HT2A) Inverse Agonist, to Treat Impulse Control Disorders in Parkinson's Disease.	Recruiting	F-CRIN	Phase 2	2020-10-23	There is no consensus on the treatment of Impulse Control Disorder (ICD) in Parkinson Disease (PD) though it is recommended to reduce the dosage of dopamine agonists (DA). Reduction of DA frequently leads to a worsening of motor signs (parkinsonism or dyskinesias due to the concomitant increase of levodopa doses) and non-motor signs with the appearance of a DA withdrawal syndrome (DAWS). Chronic stimulation of the sub-thalamic nuclei may reduce ICD but is restricted to a minority of patients and cases of new-onset ICD symptoms post stimulation have been reported. The benefit of amantadine in pathological gambling is controversial and the efficacy of clozapine has been reported in a few cases but with serious safety limitations. Very recently, naltrexone did not significantly improve ICD. Thus, an efficacious and safe treatment of ICD in PD remains an unmet need for clinical practice. Recently, it has been reported that pimavanserin, a selective serotonin 5-HT2A inverse agonist with a satisfactory safety profile without motor side effects, was efficient in improving psychosis, insomnia and day-time sleep in PD. Pimavanserin, marketed under the tradename NUPLAZID® was approved in 2016 by the U.S. Food and Drug Administration (FDA) for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. The link between serotonin and ICD has been well established, since the enhancement of 5HT2A receptors stimulation is associated to ICD, since serotonin modulates mesolimbic dopaminergic reward system transmission and given that serotonin neurotransmission is increased during chronic intake of dopamine agonist such as pramipexole which is well-known to induce ICD in PD patients. Thus, there is a large body of evidence suggesting that the decrease of the 5HT2A activity could be efficient in reducing ICD in PD. This further supports the concept of testing the efficacy of pimavanserin (a selective 5HT2A inverse agonist) for treating ICD in PD. Our aim is to conduct a study evaluating the efficacy and safety of pimavanserin on ICD in PD. This clinical trial is conducted with the support of the French NS-Park/FCRIN (French Clinical Research Infrastructure Network) network.
NCT03947216 ↗	Randomized Placebo Controlled Trial Evaluating the Efficacy of Pimavanserin, a Selective Serotonin 5-HydroxyTryptamine-2A (5HT2A) Inverse Agonist, to Treat Impulse Control Disorders in Parkinson's Disease.	Recruiting	NS-PARK	Phase 2	2020-10-23	There is no consensus on the treatment of Impulse Control Disorder (ICD) in Parkinson Disease (PD) though it is recommended to reduce the dosage of dopamine agonists (DA). Reduction of DA frequently leads to a worsening of motor signs (parkinsonism or dyskinesias due to the concomitant increase of levodopa doses) and non-motor signs with the appearance of a DA withdrawal syndrome (DAWS). Chronic stimulation of the sub-thalamic nuclei may reduce ICD but is restricted to a minority of patients and cases of new-onset ICD symptoms post stimulation have been reported. The benefit of amantadine in pathological gambling is controversial and the efficacy of clozapine has been reported in a few cases but with serious safety limitations. Very recently, naltrexone did not significantly improve ICD. Thus, an efficacious and safe treatment of ICD in PD remains an unmet need for clinical practice. Recently, it has been reported that pimavanserin, a selective serotonin 5-HT2A inverse agonist with a satisfactory safety profile without motor side effects, was efficient in improving psychosis, insomnia and day-time sleep in PD. Pimavanserin, marketed under the tradename NUPLAZID® was approved in 2016 by the U.S. Food and Drug Administration (FDA) for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. The link between serotonin and ICD has been well established, since the enhancement of 5HT2A receptors stimulation is associated to ICD, since serotonin modulates mesolimbic dopaminergic reward system transmission and given that serotonin neurotransmission is increased during chronic intake of dopamine agonist such as pramipexole which is well-known to induce ICD in PD patients. Thus, there is a large body of evidence suggesting that the decrease of the 5HT2A activity could be efficient in reducing ICD in PD. This further supports the concept of testing the efficacy of pimavanserin (a selective 5HT2A inverse agonist) for treating ICD in PD. Our aim is to conduct a study evaluating the efficacy and safety of pimavanserin on ICD in PD. This clinical trial is conducted with the support of the French NS-Park/FCRIN (French Clinical Research Infrastructure Network) network.
NCT03947216 ↗	Randomized Placebo Controlled Trial Evaluating the Efficacy of Pimavanserin, a Selective Serotonin 5-HydroxyTryptamine-2A (5HT2A) Inverse Agonist, to Treat Impulse Control Disorders in Parkinson's Disease.	Recruiting	University Hospital, Strasbourg, France	Phase 2	2020-10-23	There is no consensus on the treatment of Impulse Control Disorder (ICD) in Parkinson Disease (PD) though it is recommended to reduce the dosage of dopamine agonists (DA). Reduction of DA frequently leads to a worsening of motor signs (parkinsonism or dyskinesias due to the concomitant increase of levodopa doses) and non-motor signs with the appearance of a DA withdrawal syndrome (DAWS). Chronic stimulation of the sub-thalamic nuclei may reduce ICD but is restricted to a minority of patients and cases of new-onset ICD symptoms post stimulation have been reported. The benefit of amantadine in pathological gambling is controversial and the efficacy of clozapine has been reported in a few cases but with serious safety limitations. Very recently, naltrexone did not significantly improve ICD. Thus, an efficacious and safe treatment of ICD in PD remains an unmet need for clinical practice. Recently, it has been reported that pimavanserin, a selective serotonin 5-HT2A inverse agonist with a satisfactory safety profile without motor side effects, was efficient in improving psychosis, insomnia and day-time sleep in PD. Pimavanserin, marketed under the tradename NUPLAZID® was approved in 2016 by the U.S. Food and Drug Administration (FDA) for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. The link between serotonin and ICD has been well established, since the enhancement of 5HT2A receptors stimulation is associated to ICD, since serotonin modulates mesolimbic dopaminergic reward system transmission and given that serotonin neurotransmission is increased during chronic intake of dopamine agonist such as pramipexole which is well-known to induce ICD in PD patients. Thus, there is a large body of evidence suggesting that the decrease of the 5HT2A activity could be efficient in reducing ICD in PD. This further supports the concept of testing the efficacy of pimavanserin (a selective 5HT2A inverse agonist) for treating ICD in PD. Our aim is to conduct a study evaluating the efficacy and safety of pimavanserin on ICD in PD. This clinical trial is conducted with the support of the French NS-Park/FCRIN (French Clinical Research Infrastructure Network) network.
NCT04188392 ↗	Pimavanserin for Insomnia In Veterans With Posttraumatic Stress Disorder	Recruiting	Baylor College of Medicine	Phase 4	2020-01-06	This preliminary, open-label study assesses the feasibility of 34mg at bedtime for 6 weeks in Veterans with Posttraumatic Stress Disorder and insomnia.
NCT04292223 ↗	Open-Label Study With Pimavanserin on Activities of Daily Living in Subjects With Parkinson's Disease Psychosis	Recruiting	ACADIA Pharmaceuticals Inc.	Phase 4	2020-02-10	To assess the effect of pimavanserin on the activities of daily living in subjects with Parkinson's Disease Psychosis

Clinical Trial Conditions for NUPLAZID

Condition Name

Condition Name for NUPLAZID
Intervention	Trials
Irritability Associated With Autism Spectrum Disorder	2
Parkinson Disease	2
Parkinson Disease Psychosis	2
Post-traumatic Stress Disorder	2

Condition MeSH

Condition MeSH for NUPLAZID
Intervention	Trials
Parkinson Disease	4
Stress Disorders, Traumatic	3
Stress Disorders, Post-Traumatic	3
Sleep Initiation and Maintenance Disorders	3

Clinical Trial Locations for NUPLAZID

Trials by Country

Trials by Country for NUPLAZID
Location	Trials
United States	22
India	1
France	1

Trials by US State

Trials by US State for NUPLAZID
Location	Trials
Texas	6
Nevada	2
Ohio	2
Virginia	1
Tennessee	1

Clinical Trial Progress for NUPLAZID

Clinical Trial Phase

Clinical Trial Phase for NUPLAZID
Clinical Trial Phase	Trials
PHASE1	1
Phase 4	4
Phase 2/Phase 3	2

Clinical Trial Status

Clinical Trial Status for NUPLAZID
Clinical Trial Phase	Trials
Not yet recruiting	5
Recruiting	5
COMPLETED	2

Clinical Trial Sponsors for NUPLAZID

Sponsor Name

Sponsor Name for NUPLAZID
Sponsor	Trials
ACADIA Pharmaceuticals Inc.	6
Baylor College of Medicine	2
NS-PARK	1

Sponsor Type

Sponsor Type for NUPLAZID
Sponsor	Trials
Other	12
Industry	7
U.S. Fed	1

Clinical Trials Update, Market Analysis, and Projection for NUPLAZID (Pimavanserin)

Last updated: November 2, 2025

Introduction

NUPLAZID (pimavanserin) is an atypical antipsychotic developed by Acadia Pharmaceuticals, primarily approved for treating Parkinson’s disease psychosis (PDP). With its unique mechanism targeting serotonin receptors rather than dopamine, NUPLAZID offers a novel approach within neuropsychiatric therapeutics. As the global landscape evolves, stakeholders require comprehensive insights into its clinical development, market trajectory, and future prospects. This report synthesizes the latest clinical trials, market dynamics, and projections to guide strategic decisions.

Clinical Trials Update

Recent and Ongoing Clinical Trials

NUPLAZID’s clinical development remains active, focusing on expanding indications, optimizing efficacy, and safety profiles. Recent updates include:

• Parkinson’s Disease Psychosis (PDP):
  The FDA-approved indication stems from pivotal Phase III HARMONY trial (NCT02977655), which demonstrated significant reductions in psychosis symptoms with minimal motor symptom worsening over 6-week treatment periods. Regulatory filings for supplemental approvals aim to establish broader use and label expansion.

• Schizophrenia and Other Psychoses:
  Multiple trials, including Phase II and Phase III studies, investigate pimavanserin’s efficacy for schizophrenia and secondary psychotic symptoms in neurodegenerative disorders. Although results have been mixed, some studies have reported improvements in negative symptoms and social cognition, fueling hopes for expansion beyond PDP [1].

• Alzheimer’s Disease:
  Several ongoing Phase II studies assess pimavanserin’s potential to alleviate agitation and psychosis in Alzheimer’s patients. While initial data indicate tolerability, efficacy results are pending further analysis, which could position pimavanserin as a differentiated therapy for neuropsychiatric symptoms across neurodegenerative diseases.

• Other Neuropsychiatric Conditions:
  Trials exploring mood disorders, such as major depressive disorder with psychotic features, and obsessive-compulsive disorder are underway, yet remain in early phases, illustrating potential future growth areas.

Regulatory Developments and Data Transparency

Recent regulatory engagements include:

• Submission of sNDA (Supplemental New Drug Application) for additional indications.
• Positive feedback from the FDA on key trial data, endorsing potential label expansions.
• Increased transparency with publication of trial results in peer-reviewed journals, fostering scientific credibility.

Clinical Trial Challenges

Despite promising developments, challenges persist:

• Variability in trial outcomes, especially in off-label indications.
• The relatively small patient populations for some neurodegenerative conditions complicating recruitment.
• Need for longer-term safety data to support expanded use.

Market Analysis

Current Market Landscape

NUPLAZID operates within a niche but expanding market:

• Parkinson’s Disease Psychosis:
  Estimated to affect approximately 50% of Parkinson’s disease patients as the disease progresses, translating to a sizable population (~1 million globally). The unmet need for effective, tolerable antipsychotics with minimal motor side effects underpins NUPLAZID’s market position.

• Neuropsychiatric Disorders with Psychosis:
  The broader antipsychotic market for schizophrenia exceeds $15 billion globally, though NUPLAZID’s share remains modest due to limited indications and competition from established drugs like risperidone and clozapine.

• Neurodegenerative and Psychiatric Comorbidities:
  Growing prevalence of Alzheimer’s disease and other dementias in aging populations drives demand for novel symptomatic therapies. NUPLAZID’s potential role in treating agitation and psychosis offers a promising expansion opportunity, given the limited effective options.

Market Drivers

• Rising Prevalence of Parkinson’s Disease:
  Aging demographics forecast a 30% increase in Parkinson’s incidence globally by 2040, scaling up market potential.

• Unmet Needs in SD Psychosis:
  Traditional antipsychotics often worsen motor symptoms or cause intolerable side effects, positioning NUPLAZID as a preferred alternative.

• Regulatory Incentives:
  Orphan drug designation and fast-track approvals facilitate quicker market access and commercialization.

Competitive Landscape

Current competitors include:

• Clozapine and quetiapine, off-label for PDP but with notable safety issues.
• Emerging drugs targeting serotonin pathways or novel mechanisms, such as brexpiprazole, though none are specifically approved for PDP.

NUPLAZID’s unique serotonin 2A inverse agonist mechanism grants a competitive advantage in tolerability and safety, differentiating it from traditional dopaminergic antipsychotics.

Market Challenges

• Limited reimbursement coverage in some regions.
• Off-label use restrictions due to limited broader indication approvals.
• Ongoing need for real-world data to confirm long-term safety and efficacy.

Market Projection and Future Outlook

Forecast Assumptions

• Market Penetration:
  Initially modest due to current indication limitations, with projected growth driven by successful label expansions and evolving clinical acceptance.

• Revenue Growth:
  Industry forecasts suggest modest revenue of approximately $100-200 million globally in the near term (next 2-3 years). Long-term projections, contingent on approval for additional indications, could exceed $500 million annually by 2030.

• Regional Expansion:
  North America remains the primary market, with Europe and Asia expected to contribute significantly following regulatory approvals and clinical acceptance.

Key Growth Drivers

• Label Expansion Approvals:
  Particularly for Alzheimer’s disease psychosis, schizophrenia, and mood disorders.

• Real-World Evidence (RWE):
  Enhanced safety and efficacy data will support broader prescriber confidence.

• Clinical Pipeline Success:
  Positive trial results in early-phase studies could lead to new indications, further augmenting revenue streams.

Risks and Constraints

• Regulatory delays or rejections could impede growth.
• Competitive dynamics from emerging therapeutics.
• The potential for safety concerns emerging from larger real-world use.

Long-Term Outlook

Considering demographic trends, the high unmet medical need, and the ongoing clinical development pipeline, NUPLAZID is poised for steady growth. The key hinges on successful indication expansion and adoption in broader neuropsychiatric contexts. Strategic partnerships and sustained R&D investments will significantly influence market trajectory.

Key Takeaways

• Clinical Development:
  NUPLAZID remains actively evaluated across multiple neuropsychiatric indications, with ongoing trials potentially broadening its therapeutic footprint beyond Parkinson’s disease psychosis.

• Market Opportunity:
  The growing prevalence of neurodegenerative and psychiatric disorders presents a substantial untapped market, especially with label expansions and emerging evidence.

• Competitive Positioning:
  Its unique mechanism grants NUPLAZID a differentiating advantage, particularly in treating motor-symptom-neutral psychosis in neurodegenerative conditions.

• Forecast & Strategy:
  Near-term revenues are modest but expected to grow significantly with regulatory milestones. Stakeholders should focus on supporting broader clinical trial success, driving adoption, and expanding approvals.

• Risks:
  Regulatory hurdles, competition, and the need for robust long-term safety data remain potential challenges.

FAQs

1. What are the primary indications approved for NUPLAZID?
   NUPLAZID is primarily approved for Parkinson’s disease psychosis in adults, providing a serotonin receptor-based alternative to traditional antipsychotics.

2. Are there ongoing trials for NUPLAZID in other neuropsychiatric conditions?
   Yes. Trials are ongoing for schizophrenia, Alzheimer’s disease agitation, and other neurodegenerative-related psychoses, with preliminary data promising but not yet definitive.

3. What is the market outlook for NUPLAZID in the next five years?
   The outlook is cautiously optimistic, with potential revenues increasing if label extensions are approved and clinical data support broader use, possibly reaching over $500 million annually by 2030.

4. What factors could accelerate NUPLAZID’s market penetration?
   Successful indication expansions, positive real-world evidence, favorable regulatory outcomes, and clinician awareness are crucial.

5. What are the main competitors for NUPLAZID?
   Currently, conventional antipsychotics like risperidone and quetiapine, though not directly approved for PDP, are used off-label. Emerging therapies targeting serotonin pathways may challenge its market share in the future.

References

[1] Acadia Pharmaceuticals. (2021). NUPLAZID (pimavanserin) clinical trial results and updates.
[2] Market forecasts and industry reports, GlobalData, 2022.
[3] FDA approvals and drug labels, FDA.gov, 2022.
[4] Alzheimer’s Association. (2022). Neuropsychiatric symptoms in Alzheimer’s disease.
[5] ClinicalTrials.gov. (2022). List of ongoing pimavanserin clinical trials.