Acadia’s Nuplazid has failed to hit a statistical significance on the primary endpoint in a pivotal, large-scale phase 3 study for major depressive disorder (MDD), despite showing promise in an earlier, smaller trial.
The 298-patient phase 3 CLARITY study combined two identical, double-blind, placebo-controlled studies evaluating the efficacy, safety and tolerability of Nuplazid (pimavanserin) as an additional therapy for MDD.
Participants were randomised to receive either Nuplazid or placebo each day for six weeks, given as an add-on treatment to the antidepressants they were already receiving. The drug failed to improve patient scores on the Hamilton Depression Rating Scale (HAMD-17) – a standard measure used for depression and the primary endpoint of the study.
The drug managed to meet the key secondary endpoint of a slim improvement on Clinical Global Impression – Severity (CGI-S) score, used to determine the severity of a patient’s depression. Nuplazid was also found to be generally safe to use, with the most common side effects including diarrhoea, dry mouth and headache.
“We observed a consistent improvement of depressive symptoms over time with Nuplazid but, unfortunately, the robust positive results from our CLARITY-1 study were not replicated,” said Serge Stankovic, president of Acadia.
“While these results do not support the product profile to pursue an additional phase 3 study in adjunctive MDD, we will continue to analyse the data and the findings from our earlier positive depression studies as we assess the next steps,” he added.
In 2016, Acadia won US Food and Drug Administration (FDA) approval for Nuplazid as a treatment for Parkinson’s disease-associated psychosis, the first therapy approved in this setting. The company has also submitted an application for the drug for the treatment of hallucinations and delusions associated with dementia-related psychosis to the FDA, with an action data set for 3 April 2021.
Last year, the drug also failed a late-stage trial in schizophrenia inadequately controlled by currently-approved drugs. In this trial, Nuplazid was unable to show a significant improvement compared to placebo on the widely-used Positive and Negative Symptoms of Schizophrenia (PANSS) scale.
The schizophrenia trial, like the MDD trial, was viewed as one of Acadia’s biggest opportunities to extend the Nuplazid franchise – currently the company’s only approved medicine.