25 Jul Pimavanserin Therapy in Elderly Patients with Neurodegenerative Disease-Related Neuropsychiatric Symptoms : Safety Study
MedicalResearch.com Interview with:
Dr. Gus Alva
Gus Alva, MD, DFAPA
Medical Director, ATP Clinical Research
Medical Director, Senior Brain Health, Hoag Hospital, Newport Beach,
Assistant Professor, Department of Psychiatry and Neuroscience
University of California, Riverside, CA
MedicalResearch.com: What is the background for this study?
Response: This trial evaluated the effects of pimavanserin compared to placebo in frail older adults and elderly patients with neuropsychiatric symptoms related to Neurodegenerative disorder (NDD), such as hallucinations and delusions, to better understand the safety of pimavanserin in this population.
The study was a phase 3b, 8-week treatment (study duration of up to 16 weeks) with the primary endpoint being safety and tolerability, measured by treatment-emergent adverse events (TEAEs). Secondary safety endpoints were change from baseline in motor and cognitive function; exploratory endpoints included suicidality, sleep quality, and neuropsychiatric symptoms.
The reason for doing this study is that there is a high degree of interest in further understanding the safety of pimavanserin, as many antipsychotics used off label often have significant and serious adverse effects, including risk of falls, parkinsonism, and death.
MedicalResearch.com: How does Pimavanserin differ from other medications for neuropsychiatric symptoms in neurodegenerative diseases?
Response: Pimavanserin is a 5HT2-A inverse agonist/antagonist, meaning that it is the only current atypical antipsychotic that doesn’t directly antagonize D2 receptors in the brain and is the only medication currently FDA approved to treat Parkinson’s Disease Psychosis (PDP). This trial demonstrated that pimavanserin is well tolerated in older adults and frail elderly patients with neuropsychiatric symptoms related to NDD, including Parkinson’s disease (with or without dementia) and other forms of dementia, including Alzheimer’s disease, dementia with Lewy bodies, and all-cause dementia. These results support the previously established safety profile of pimavanserin and further inform its use in patients with PDP.
MedicalResearch.com: What are the main findings?
Response: Incidences of TEAEs were similar between treatment groups; 29.8% reported ≥1 TEAE (pimavanserin: 30.4%; placebo: 29.3%), and 1.8% reported serious TEAEs (pimavanserin: 2.0%; placebo: 1.5%).
Pimavanserin did not impact motor or cognitive-related function. This trial demonstrated that pimavanserin is well tolerated in older adults and frail elderly patients with neuropsychiatric symptoms related to NDD, including Parkinson’s disease (with or without dementia) and other forms of dementia, including Alzheimer’s disease, dementia with Lewy bodies, and all-cause dementia.
These results support the previously established safety profile of pimavanserin and further inform its use in patients with PDP.
Treatment with pimavanserin was also not associated with cognitive decline (measured using the MMSE) or motor dysfunction (measured using the ESRS-A). This lack of cognitive or motor function- related side effects further highlight the safety and tolerability of pimavanserin. In addition, there were similar rates of suicidal ideation in both the pimavanserin (n = 4; 1.1%) and placebo (n = 1; 0.3%) groups. Notably, treatment with pimavanserin improved sleep quality, and improvement was also seen in neuropsychiatric symptoms in the CGI-I.
MedicalResearch.com: What should readers take away from your report?
Response: Pimavanserin is a well-tolerated medication and not associated with motor or cognitive impairment in patients with NDD. Our findings highlight the manageable and generally favorable safety profile of pimavanserin in patients with NDD, contributing to our knowledge on the safety of pimavanserin as it generalizes to patients with PDP.
MedicalResearch.com: What recommendations do you have for future research as a results of this study?
Response: Since patients were also eligible to participate in a 52-week, open-label extension study, this study will further inform safety and tolerability in a longer-term time interval in this patient population.
MedicalResearch.com: Is there anything else you would like to add? Any disclosures?
Response: 1,440 patients were screened; of these, 730 completed the study (93.1%), and 54 patients (6.9%) terminated the study early. The most common reason for study termination was AEs (n=16; 2.0%), including cardiac disorders, infections, injuries, and nervous system disorders. A key strength of this study is its large sample size and the fact that this study also evaluated patients across multiple clinical sites in several global regions
Disclosures:
- Research Support from Abbvie, Accera, Axsome, Axovant, Biogen, Eisai, Eli-Lily, Neurotrope, Genentech, Intra Cellular, Janssen, Lundbeck, Neurim, Novartis, Otsuka, Roche, Sage, Suven, and Trans Tech.
- Speakers Bureau and Consultant for Abbvie, Acadia, Alkermes, Axsome, Biogen, Janssen, Idorsia, Lundbeck, Myriad, Neurocrine, Nestle, Otsuka, Sage, Sunovion, Teva and Takeda
Citation: Alva G, Cubała WJ, Berrio A, Coate B, Abler V, Pathak S. Safety Profile of Pimavanserin Therapy in Elderly Patients with Neurodegenerative Disease-Related Neuropsychiatric Symptoms: A Phase 3B Study. J Alzheimers Dis. 2024;98(1):265-274. doi: 10.3233/JAD-231167. PMID: 38427485; PMCID: PMC10977351.
The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition.
Some links may be sponsored. Products are not warranted or endorsed.
Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.
Last Updated on August 2, 2024 by Marie Benz MD FAAD