Pimavanserin – Schizophrenia Inadequate Response
Pimavanserin is a proprietary small molecule that we have advanced to Phase III development for schizophrenia patients with an inadequate response to current antipsychotic therapy. 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 Mental Health Institute, approximately one percent of the U.S. population develops schizophrenia during their lifetime. Schizophrenia is a chronic, debilitating 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. Current drugs used to treat schizophrenia have substantial limitations, including severe side effects and a lack of efficacy on the full range of symptoms of the disease.
According to the American Psychiatric Association, about 30 percent of patients with schizophrenia have an inadequate response to antipsychotic medications, meaning that they exhibit some improvement, but who continue to have psychotic symptoms. As a result, about 25 to 50 percent of schizophrenia patients are treated with two or more antipsychotics. This polypharmacy has led to increased dose-related side effects and complicated dosing regimens that can further contribute to poor treatment compliance and subsequent relapse in these patients.
We are currently conducting a Phase III, six-week, randomized, double-blind, placebo-controlled, multi-center, outpatient study, referred to as the ENHANCE-1 study, designed to examine the efficacy and safety of adjunctive use of pimavanserin in patients with schizophrenia who have not achieved an adequate response to their current antipsychotic treatment. Approximately 380 patients will be randomized to receive pimavanserin or placebo, orally, once daily, in addition to their ongoing antipsychotic medication in a flexible dosing regimen. The starting daily 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 six on the Positive and Negative Syndrome Scale (PANSS) total score.