Pimavanserin – Schizophrenia Negative Symptoms
Pimavanserin is a proprietary small molecule that we have advanced to Phase II development for negative symptoms of schizophrenia. Pimavanserin is a selective serotonin inverse agonist (SSIA) preferentially targeting 5-HT2A receptors. Its distinct mechanism of action targets serotonergic 5-HT2A receptors while avoiding activity at dopamine and other receptors commonly targeted by other antipsychotics.
According to the National Institute of Mental Health, approximately one percent of the U.S. population develops schizophrenia during their lifetime. Schizophrenia is a chronic, debilitating mental illness characterized by thought disorder, emotional and cognitive dysfunction, and behavioral disturbances. These disturbances may include positive symptoms, including hallucinations, delusions, and disorganized speech, as well as a range of negative symptoms, including flat affect, loss of interest, emotional withdrawal, and cognitive impairment.
Studies show that about 40 to 50 percent of schizophrenia patients suffer from prominent 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.
We are currently conducting a Phase II, 26-week, randomized, double-blind, placebo-controlled, multi-center study, referred to as the ADVANCE study, designed to examine the efficacy and safety of adjunctive use of pimavanserin in patients with schizophrenia who have predominant negative symptoms. Approximately 380 patients will be randomized to receive either pimavanserin or placebo, orally, once daily, in addition to their ongoing antipsychotic medication in a flexible dosing regimen. The starting dose of 20 mg of pimavanserin at baseline may be adjusted to 34 mg or 10 mg during the first three weeks of treatment. The primary endpoint of the study is the change from baseline to week 26 on the Negative Symptom Assessment-16 (NSA-16) total score.