Pimavanserin – Schizophrenia Negative Symptoms
Pimavanserin is a proprietary small molecule that we have advanced to Phase 3 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.
In November 2019, we announced positive top-line results from the pivotal Phase 2 ADVANCE study, a 26-week, randomized, double-blind, placebo-controlled study of 403 patients with predominantly negative symptoms of schizophrenia who achieved adequate control of their positive symptoms while taking existing antipsychotic. In the study, pimavanserin compared to placebo demonstrated a statistically significant improvement on the study’s primary endpoint, change from baseline to week 26 on the Negative Symptom Assessment-16 (NSA-16) total score.
Acadia plans to commence a second pivotal study in the first half of 2020. No drug is approved by the FDA for the treatment of the negative symptoms of schizophrenia.
Information presented above is related to an investigational use of pimavanserin. Pimavanserin is not approved by the FDA for the treatment of negative symptoms of schizophrenia. Please see below FDA approved indication for pimavanserin, including Important Safety Information & Boxed WARNING.
Important Safety Information and Indication for NUPLAZID (pimavanserin)
- Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
- NUPLAZID is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson’s disease psychosis.
- Contraindication: NUPLAZID is contraindicated in patients with a history of a hypersensitivity reaction to pimavanserin or any of its components. Rash, urticaria, and reactions consistent with angioedema (e.g., tongue swelling, circumoral edema, throat tightness, and dyspnea) have been reported.
- QT Interval Prolongation: NUPLAZID prolongs the QT interval.
- The use of NUPLAZID should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong QT interval including Class 1A antiarrhythmics or Class 3 antiarrhythmics, certain antipsychotic medications, and certain antibiotics.
- NUPLAZID should also be avoided in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and presence of congenital prolongation of the QT interval.
- Adverse Reactions: The most common adverse reactions (≥2% for NUPLAZID and greater than placebo) were peripheral edema (7% vs 2%), nausea (7% vs 4%), confusional state (6% vs 3%), hallucination (5% vs 3%), constipation (4% vs 3%), and gait disturbance (2% vs <1%).
- Drug Interactions:
- Coadministration with strong CYP3A4 inhibitors (e.g., ketoconazole) increases NUPLAZID exposure. Reduce NUPLAZID dose to 10 mg taken orally as one tablet once daily.
- Coadministration with strong or moderate CYP3A4 inducers reduces NUPLAZID exposure. Avoid concomitant use of strong or moderate CYP3A4 inducers with NUPLAZID.
Indication: NUPLAZID is indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis.
Dosage and Administration: Recommended dose: 34 mg capsule taken orally once daily, without titration.
NUPLAZID is available as 34 mg capsules and 10 mg tablets.
Please see full Prescribing Information including Boxed WARNING for NUPLAZID.