Nuplazid (pimavanserin) for the treatment of Parkinson’s Disease Psychosis (PDP), United States of America
Nuplazid (pimavanserin), a selective serotonin inverse antagonist (SSIA), is an investigational drug for the treatment of Parkinson's Disease Psychosis (PDP).
The drug was discovered and developed by Acadia Pharmaceuticals.
The US Food and Drug Administration (FDA) granted breakthrough therapy designation for the drug for the treatment of PDP in 2014.
The new drug application (NDA) of Nuplazid for the treatment of PDP was accepted and granted priority review status by the FDA in November 2015. The FDA set May 2016 as the Prescription Drug User Fee Act (PDUFA) action date for Nuplazid.
If approved by the FDA, Nuplazid will become the first drug for the treatment of psychosis associated with Parkinson's disease.
Psychosis in Parkinson's disease
Parkinson's disease is an acute neurodegenerative disorder caused by the degeneration of neurons in the primary motor cortex or M1 region of the brain. Psychosis in Parkinson's disease (PDP) is a debilitating disorder that occurs in approximately 40% of patients with PD.
PDP is characterised by the occurrence of hallucinations and delusions, which can be burdensome to PD patients as it affects their quality of life.
According to estimates by the National Parkinson Foundation, approximately one million people in the US and between four and six million people worldwide are affected by PDP.
Nuplazid's mechanism of action
Nuplazid contains a non-dopaminergic anti-psychotic drug that contains a selective serotonin inverse agonist (SSIA). It mainly blocks 5-HT2A receptors and also helps in terminating psychosis symptoms associated with PD.
The drug will be available for oral administration.
Clinical trials on Nuplazid
The new drug application of Nuplazid was submitted to the FDA based on results obtained from a Phase III clinical trial known as 020 study, which was conducted between August 2010 and August 2012.
The six-week double-blind, placebo-controlled study enrolled 199 PDP patients over the age of 40. Nuplazid was administered to 95 recipients, while 90 patients received placebo.
Primary outcome measure of the study was anti-psychotic benefit, which was assessed by central, independent raters with the Parkinson's disease-adapted scale for assessment of positive symptoms (SAPS-PD).
Results of the study demonstrated that patients treated with Nuplazid showed statistical improvement on all primary and secondary efficacy endpoints with no worsening of motor function. The study also showed that patients treated with Nuplazid were associated with a -5.79 decrease in SAPS-PD scores, compared with -2.73 for placebo.
Nuplazid showed a marked improvement in all domains such as hallucinations, delusions, secondary psychoses and night-time sleep. The results were harmonious across all subgroups, indicating greater enhancement with Nuplazid over placebo regardless of sex, race and age group.
Acadia Pharmaceuticals started another Phase III clinical trial on Nuplazid by enrolling 500 patients in July 2007. It is a multi-centre, open label extension study intended to evaluate the safety and tolerability of Nuplazid in patients with PDP.