Synonyms: Nuplazid, ACP-103, Pimavanserin tartrate
Therapy Type: Small Molecule (timeline)
Target Type: Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease, Schizophrenia
U.S. FDA Status: Alzheimer's Disease (Phase 2), Schizophrenia (Phase 3)
Company: Acadia Pharmaceuticals
Approved for: Parkinson's psychosis
Pimavanserin is a serotonergic agent, specifically a selective serotonin (5-HT) 2A receptor inverse agonist. In April 2016, the FDA approved this once-daily drug to treat the delusions and hallucinations that are a feature of psychosis in Parkinson's disease, and it came on the market in the United States in June (April 2016 news, prescribing information). Pimavanserin is thought to have fewer adverse effects than older antipsychotic agents used to treat Parkinson's psychosis (e.g., Sarva and Henchcliffe, 2016).
Pimavanserin is in Phase 2 development for psychosis, agitation, and aggression in Alzheimer's disease (below), and is in Phase 3 development for schizophrenia. A different serotonin 2A receptor inverse agonist, nelotanserin, is in Phase 2 development for dementia with Lewy bodies (DLB).
Between November 2014 and November 2016, Acadia conducted a Phase 2 study of pimavanserin in 181 London-based nursing home residents who had symptoms of psychosis along with their clinical diagnosis of AD. Participants received a 12-week course of 40 mg pimavanserin or placebo, and were evaluated on the nursing home version of the neuropsychiatric inventory (NPI), the short form of the Cohen-Mansfield Agitation Inventory (CMAI-SF), and the Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC).
In June 2016, Acadia registered a trial in 306 people who have clinical agitation and aggression along with their mild to moderate Alzheimer's disease. To be conducted in six European and South American countries and the United States, this trial enrolls patients living at home or in assisted living facilities. The study evaluates a 12-week course of 40 mg pimavanserin against placebo for change on the NPI combined agitation and aggression score of the NPI Clinician rating scale, as well as for change on an NPI measure of caregiver distress. The trial will offer an open-label extension, but as of November 2016, was not yet listed on clinicatrials.gov.
- Sarva H, Henchcliffe C. Evidence for the use of pimavanserin in the treatment of Parkinson's disease psychosis. Ther Adv Neurol Disord. 2016 Nov;9(6):462-473. Epub 2016 Oct 3 PubMed.
- Subudhi BB, Sahu PK. Angiotensin Mediated Oxidative Stress and Neuroprotective Potential of Antioxidants and AT1 Receptor Blockers. Mini Rev Med Chem. 2016 Oct 24; PubMed.
- Liu J, Liu S, Tanabe C, Maeda T, Zou K, Komano H. Differential effects of angiotensin II receptor blockers on Aβ generation. Neurosci Lett. 2014 May 1;567:51-6. Epub 2014 Mar 27 PubMed.
- Torika N, Asraf K, Danon A, Apte RN, Fleisher-Berkovich S. Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies. PLoS One. 2016;11(5):e0155823. Epub 2016 May 17 PubMed.
- Böhm M, Schumacher H, Leong D, Mancia G, Unger T, Schmieder R, Custodis F, Diener HC, Laufs U, Lonn E, Sliwa K, Teo K, Fagard R, Redon J, Sleight P, Anderson C, O'Donnell M, Yusuf S. Systolic blood pressure variation and mean heart rate is associated with cognitive dysfunction in patients with high cardiovascular risk. Hypertension. 2015 Mar;65(3):651-61. Epub 2015 Jan 12 PubMed.
- Li W, Zhang JW, Lu F, Ma MM, Wang JQ, Suo AQ, Bai YY, Liu HQ. [Effects of telmisartan on the level of Aβ1-42, interleukin-1β, tumor necrosis factor α and cognition in hypertensive patients with Alzheimer's disease]. Zhonghua Yi Xue Za Zhi. 2012 Oct 23;92(39):2743-6. PubMed.
- Shindo T, Takasaki K, Uchida K, Onimura R, Kubota K, Uchida N, Irie K, Katsurabayashi S, Mishima K, Nishimura R, Fujiwara M, Iwasaki K. Ameliorative effects of telmisartan on the inflammatory response and impaired spatial memory in a rat model of Alzheimer's disease incorporating additional cerebrovascular disease factors. Biol Pharm Bull. 2012;35(12):2141-7. PubMed.