Acadia Pharmaceuticals announced positive top-line results from its phase 2 ADVANCE study, which evaluated the efficacy and safety of adjunctive pimavanserin treatment in patients with predominantly negative symptoms of schizophrenia who have achieved adequate control of positive symptoms with their existing antipsychotic treatment. No drug is approved by the FDA for the treatment of the negative symptoms of schizophrenia.
The 26-week, randomized, double-blind, placebo-controlled, multi-center, international ADVANCE Study enrolled 403 patients who were randomized to receive once-daily pimavanserin (n=201) or placebo (n=202) as an adjunct treatment to their ongoing antipsychotic in a flexible dosing regimen. The starting daily dose of 20 mg of pimavanserin at baseline was allowed to be adjusted to 34 mg or 10 mg during the first eight weeks of treatment. 53.8% of patients who were randomized to receive pimavanserin completed the trial on 34 mg, 44.7% on 20 mg, and 1.5% on 10 mg. The primary endpoint of the study was the change from baseline to week 26 on the Negative Symptom Assessment-16 (NSA-16) total score.
Pimavanserin demonstrated a statistically significant improvement on the study’s primary endpoint compared to placebo (-10.4 vs. -8.5). A greater improvement in the NSA-16 total score compared to placebo was observed in the 53.8% of patients (n=107) who received the highest pimavanserin dose of 34 mg (-11.6 vs. -8.5). Pimavanserin did not separate from placebo on the key secondary endpoint, the Personal and Social Performance (PSP) scale.
Additional results from the ADVANCE study will be presented at future scientific meetings. ACADIA plans to commence a second pivotal study with the 34 mg dose of pimavanserin in the first half of 2020.
The treatment was well tolerated. No clinically significant differences in vital signs, weight, metabolic syndrome or extrapyramidal symptoms were observed in the pimavanserin group compared to placebo.
Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors. These receptors are thought to play an important role in psychosis, schizophrenia, depression and other neuropsychiatric disorders. In vitro, pimavanserin demonstrated no appreciable binding affinity for dopamine (including D2), histamine, muscarinic, or adrenergic receptors.
The FDA approved Pimavanserin in April of 2016 for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. It is marketed under the trade name Nuplazid.
About Schizophrenia and Negative Symptoms
Schizophrenia is a chronic, debilitating and often progressive mental illness characterized by disturbances in thinking, emotional reaction, and behavior. These disturbances may include positive symptoms, such as hallucinations and delusions, and a range of negative symptoms, including loss of interest, emotional withdrawal, and cognitive disturbances.
Studies show that about 40 to 50 percent of schizophrenia patients suffer from predominant negative symptoms. While currently available antipsychotic treatments for schizophrenia target positive symptoms, most patients remain functionally impaired because of negative symptoms, cognitive deficits, and limited social function.