Nuplazid (pimavanserin) / Acadia Pharma - LARVOL DELTA

US appeals court confirms patent validity of Acadia's Parkinson's drug (Reuters) - "Acadia Pharmaceuticals...said on Monday that the U.S. Court of Appeals has confirmed the validity of its patent for Nuplazid, its drug for hallucinations and delusions associated with Parkinson's disease. The decision supports a December 2023 ruling from the U.S. District Court of Delaware, ensuring the patent remains protected in Acadia's legal battle against India-based drugmaker MSN Laboratories."

Patent • Parkinson's Disease

Sedation and sleep safety of pimavanserin for Parkinsons's disease psychosis: Review and exploratory analysis of clinical study data. (PubMed, Clin Park Relat Disord) - "The results from our exploratory analyses suggest that pimavanserin may be associated with negligible levels of sedation and other sleep‑related adverse events and may provide improvements in nighttime sleep compared with placebo. Future head-to-head clinical trials will be needed for direct comparisons between pimavanserin and other atypical antipsychotics, such as quetiapine or clozapine."

Journal • Review • Alzheimer's Disease • Anesthesia • CNS Disorders • Cognitive Disorders • Hypotension • Movement Disorders • Parkinson's Disease • Psychiatry • Sleep Disorder

Persistent 5-HT2AR Signaling Triggered by Prolonged Exposure to a Serotonergic Psychedelic In Vitro (CPDD 2025) - "The 5-HT2AR antagonists/inverse agonists M100,907 and pimavanserin were employed to validate the contribution of the 5-HT2AR to agonist-initiated signaling... Our data indicate that 5-HT2AR signaling induced by prolonged (-)-DOI exposure in vitro is paradoxically sustained despite removal of the agonist from the extracellular space. Enduring 5-HT2AR signaling produced by (-)-DOI may contribute to its ameliorative effects and continuing studies will evaluate if persistent 5-HT2AR signaling supports psychoplastogenesis in vivo."

Preclinical • CNS Disorders • Psychiatry

Heads Up: A Potential Interplay Between Antipsychotic Medications Sickle Cell Trait and Priapism (APA 2025) - "He experienced priapism with aripiprazole, risperidone, paliperidone, olanzapine, and lurasidone. Despite switching to cariprazine, which has lower alpha-1 adrenergic antagonism, episodes of priapism persisted. The patient achieved partial psychiatric stabilization with a low dose of pimozide and valproate, and sildenafil was added as a preventive measure for priapism, resulting in no further episodes. Pimavanserin was not pursued due to its cost... Clinicians should be aware of this potential side effect and educate patients on the importance of reporting symptoms and seeking timely medical care. Further research is needed to clarify the mechanisms of priapism related to antipsychotic use, develop treatment protocols for managing psychosis in cases of recurrent priapism, and explore the relationship between sickle cell trait and antipsychotic-induced priapism."

Cardiovascular • CNS Disorders • Genetic Disorders • Hematological Disorders • Psychiatry • Schizophrenia • Sickle Cell Disease

The Combination of Pimavanserin and Atomoxetine Reduces Obstructive Sleep Apnea Severity: A Randomized Trial (ATS 2025) - "The combination of atomoxetine and pimavanserin significantly reduced OSA severity, lowering arousal index and overnight hypoxemia. Compared to placebo, the combination did not raise the risk of many adverse effects seen in similar trials (e.g., insomnia, headache, tachycardia), except for a mild heart rate increase. Pimavanserin shows promise to be associated to atomoxetine for treating OSA and merits further, larger trials."

Clinical • Cardiovascular • Insomnia • Obstructive Sleep Apnea • Pain • Respiratory Diseases • Sleep Disorder

Exploring the Risk of Adverse Drug Events in Combination with antiparkinsonics and antipsychotics - a two-decade real-world pharmacovigilance analysis based on the FAERS database. (PubMed, Int J Neuropsychopharmacol) - "During the combined application of antiparkinsonics and AP, in addition to ADEs such as movement disorders and emerging mental symptoms, the risks of infection and inflammation should also be given key attention. Long-term follow-up should run through the entire process of disease diagnosis and treatment, and attention should be paid to the influence of drug dosage forms and dosages. The medication plan should be adjusted in a timely manner when ADEs occur."

Adverse events • Journal • Real-world evidence • Alzheimer's Disease • CNS Disorders • Infectious Disease • Inflammation • Movement Disorders • Nephrology • Parkinson's Disease • Psychiatry • Urology

5-HT2A receptor inverse agonist attenuates morphine withdrawal syndrome and its aversiveness in rats. (PubMed, Behav Pharmacol) - "The pimavanserin injection also significantly attenuated the aversiveness of morphine withdrawal, as indicated by reduced conditioned avoidance of the chamber where precipitated withdrawal had occurred. These results indicate a major role for the 5-HT2A receptor in opiate physical dependence and withdrawal syndrome, suggesting this receptor as a potential therapeutic target."

Journal • Preclinical • Addiction (Opioid and Alcohol)

Delaware District Court Rules in Favor of Acadia in NUPLAZID (pimavanserin) Formulation Patent Litigation (Businesswire) - "Acadia Pharmaceuticals Inc...announced that the U.S. District Court for the District of Delaware ruled in favor of Acadia regarding its ‘721 formulation patent for NUPLAZID (pimavanserin), Acadia’s drug for the treatment of Parkinson’s Disease Psychosis. In today’s order, the Court ruled in favor of Acadia on both infringement and validity arguments in its formulation patent litigation against Aurobindo Pharma Limited and other ANDA (Abbreviated New Drug Application) filers....'We are very pleased with today’s decisive ruling in our favor, which provides patent protection for NUPLAZID 34 mg capsule formulation into 2038.'"

Patent • Parkinson's Disease • Psychiatry

The Modified Functional Status Questionnaire for Assessing Patients with Parkinson's Disease Psychosis Treated with Pimavanserin: A Post Hoc Analysis. (PubMed, Neurol Ther) - "This analysis provides additional information about the impact of treatment with pimavanserin on specific mFSQ subscales. Additionally, the mFSQ was significantly correlated with the patient- and the caregiver-rated Schwab and England ADL scales."

Journal • Retrospective data • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Nuplazid: “Up 23% year-over-year; highest ever quarterly sales” (Acadia) - Q1 2025 Results

Commercial • CNS Disorders • Parkinson's Disease

Acadia Pharmaceuticals Reports First Quarter 2025 Financial Results and Operating Overview (Businesswire) - "Net product sales of NUPLAZID were $159.7 million in the first quarter of 2025, an increase of 23% as compared to $129.9 million for the first quarter of 2024. The 23% year-over-year increase in net product sales of NUPLAZID included 6% volume growth in 2025 compared to 2024 and a seasonal reduction in gross to net from the Medicare Part D redesign as part of the Inflation Reduction Act."

Sales • CNS Disorders • Parkinson's Disease

Unlocking the potential of lumateperone and novel anti-psychotics for schizophrenia. (PubMed, Bioimpacts) - "This review also focuses on a few more emerging antipsychotics like brexpiprazole, brilaroxazine, roluperidone, F17464, pimavanserin (ACP-103), xanomeline, BI 409306, BI 425809 and MK-8189 which are under different phase of clinical trials and might get approved soon. All the antipsychotic drugs covered did not show any other severe adverse effects except gastrointestinal issues and cardiometabolic risk factors. However, still rigorous clinical trials and modifications are needed to manage adverse effects, and we can expect a few antipsychotics to be on the market soon."

Journal • Review • Anesthesia • CNS Disorders • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Psychiatry • Schizophrenia

Impact of pimavanserin on prescribing practices in parkinson disease. (PubMed, Clin Park Relat Disord) - "AAP dispensings were categorized into (1) pimavanserin, (2) clozapine and quetiapine (i.e., PDP-"preferred" mixed receptor antagonist AAPs), and (3) the remaining AAPs (i.e., PDP-"nonpreferred" mixed receptor antagonist AAPs). Quetiapine remained the most prescribed AAP. Comparative safety and effectiveness studies are needed to define the relative risks and benefits of treatment options in PDP."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Evaluation of Mortality in Users of Pimavanserin Compared with Other Atypical Antipsychotics in Patients with Parkinson's Disease Psychosis: An Update. (PubMed, Drug Saf) - "In the overall PDP cohort, mortality risk was lower among pimavanserin initiators than comparator antipsychotic initiators."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Extension Study of Pimavanserin in Irritability Associated With Autism Spectrum Disorder (clinicaltrials.gov) - P2/3 | N=209 | Terminated | Sponsor: ACADIA Pharmaceuticals Inc. | Trial completion date: Jul 2025 ➔ Feb 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jul 2025 ➔ Feb 2025; The study was terminated for business reasons and not due to safety concerns.

Trial completion date • Trial primary completion date • Trial termination • Autism Spectrum Disorder • Genetic Disorders

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Pimavanserin as an Adjunctive Treatment for the Negative Symptoms of Schizophrenia (ADVANCE-2) in Patients With Predominant Negative Symptoms. (PubMed, Schizophr Bull) - "In this study, pimavanserin was well tolerated, and although it demonstrated a similar treatment effect as in the prior phase 2 study favoring pimavanserin, treatment with pimavanserin vs placebo did not result in significant differences for primary or other endpoints."

Clinical • Journal • P3 data • CNS Disorders • Psychiatry • Schizophrenia

Healthcare resource utilization patterns among patients with Parkinson's disease psychosis and dementia: analysis of US Medicare beneficiaries treated with pimavanserin versus other-atypical antipsychotics or versus quetiapine. (PubMed, J Med Econ) - "Pimavanserin (PIM) is the only FDA approved atypical antipsychotic treatment (AAP) for hallucinations and delusions associated with Parkinson's disease psychosis (PDP) among patients with or without coexisting dementia; however, other AAPs (i.e., quetiapine (QUE), risperidone, olanzapine, aripiprazole) are commonly prescribed off-label. Patients initiating PIM-monotherapy for PDP + D experienced 12% lower all-cause inpatient hospitalizations vs. Other-AAPs or QUE. These results are consistent with prior real-world research in PDP with or without dementia."

HEOR • Journal • Medicare • Reimbursement • US reimbursement • Alzheimer's Disease • CNS Disorders • Dementia • Movement Disorders • Parkinson's Disease • Psychiatry

ADVANCE-2: Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia (clinicaltrials.gov) - P3 | N=454 | Completed | Sponsor: ACADIA Pharmaceuticals Inc. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Psychiatry • Schizophrenia

The combination of pimavanserin and atomoxetine reduces obstructive sleep apnea severity: a randomized crossover trial. (PubMed, Chest) - "Pimavanserin with atomoxetine is a strong pharmacological therapy candidate for OSA."

Journal • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Third-Generation Antipsychotics: The Quest for the Key to Neurotrophism. (PubMed, Life (Basel)) - "While second-generation antipsychotics (SGAs) are associated with a better side effect profile than their predecessors, the emergence of third-generation antipsychotics (TGAs)-such as brexpiprazole, cariprazine, lurasidone, iloperidone, lumateperone, pimavanserin, and roluperidone-has prompted renewed interest in their potential neuroprotective and pro-cognitive effects. Although data remain limited and focused primarily on earlier SGAs, emerging findings suggest that some TGAs may exert positive effects on neuroplastic processes, including the modulation of brain-derived neurotrophic factors (BDNFs) and synaptic architecture. However, robust clinical data on their long-term effects and comparative efficacy are lacking; therefore, further research is necessary to validate their role in preventing neurodegenerative changes and improving cognitive outcomes in patients with psychiatric conditions."

Journal • Review • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia • BDNF

Pimavanserin and Aggression and Social Cognition. (clinicaltrials.gov) - P2 | N=35 | Recruiting | Sponsor: Ohio State University | Trial completion date: Jan 2026 ➔ Jan 2028 | Trial primary completion date: Jan 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Behavior Disorders

Management of Parkinson's disease psychosis: first-line antipsychotic selection and rationale for continuing, combining, or switching. (PubMed, Expert Opin Pharmacother) - "An evidence-based review by the Movement Disorder Society found pimavanserin and clozapine to be clinically useful, (low-dose) quetiapine to be possibly useful, and all other antipsychotics to be avoided due to motor worsening. Pimavanserin is recommended as a first-line antipsychotic therapy based on its established safety and efficacy. While switching strategies are suggested, further study is needed to assess combination antipsychotic therapy."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Hypotension • Movement Disorders • Parkinson's Disease • Psychiatry

Atypical Antipsychotics for Neuropsychiatric Symptoms in Alzheimer's Disease: A Systematic Review and Meta-Analysis (AAN 2025) - "Heterogeneity was assessed with I² statistics.This study included a total of 17 RCTs with 5.018 patients, of whom 3.093 (61,64%) received either aripiprazole, brexpiprazole, olanzapine, pimavanserin, quetiapine or risperidone. Our findings indicate that atypical antipsychotics can be used for management of NPS in patients with AD, reducing the severity and incidence of agitation, without increasing SAEs and all-cause mortality. However, these drugs were not associated with the improvement in cognitive impairment."

Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Psychiatry

Challenging the impostor: a scoping review of the pharmacological management of Capgras syndrome in Parkinson's disease and Lewy bodies dementia. (PubMed, Neurol Sci) - "Although neuroleptics and dopaminergic dose adjustments appear to be beneficial for CS in PD and LBD, robust evidence is lacking. Future prospective studies are essential to establish evidence-based guidelines for this challenging syndrome."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease • Movement Disorders • Parkinson's Disease • Psychiatry

Pimavanserin for Rigid-compulsive Symptoms in Autism Spectrum Disorder (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: New York State Psychiatric Institute | Not yet recruiting ➔ Recruiting

Enrollment open • Autism Spectrum Disorder • Genetic Disorders