Vanda Pharmaceuticals Inc. has announced that BYSANTI™ (milsaperidone) tablets have been approved by the U.S. Food and Drug Administration (FDA) as a first-line treatment for acute manic or mixed episodes associated with bipolar I disorder and for the treatment of schizophrenia in adults. BYSANTI is a new chemical entity (NCE) within the atypical antipsychotic class.
BYSANTI showed bioequivalence to iloperidone in both high and low dose regimens. Iloperidone is marketed as Fanapt and has accumulated more than 100,000 patient-years of real-world clinical use. The approval allows BYSANTI to rely in part on existing clinical data regarding iloperidone’s safety and efficacy profile.
President, CEO, and Chairman of the Board of Vanda Pharmaceuticals, Mihael H. Polymeropoulos, M.D., has commented on the approval as a significant step forward in the lives of patients and providers. According to him, BYSANTI represents a dependable new treatment option built upon a longstanding clinical legacy and reflects an accelerated innovation model in pharmaceutical development aimed at addressing unmet needs in behavioral health.
BYSANTI (milsaperidone) rapidly interconverts to iloperidone, which produces two active molecules. The drug is an antagonist of the dopamine D2, serotonin 5-HT2A, and alpha1-adrenergic receptors, which are involved in the neurochemical pathways associated with schizophrenia and bipolar I disease. Its safety profile is reported to be similar to that of iloperidone.
The drug’s receptor-binding profile shows relatively higher affinity for alpha-adrenergic receptors compared with dopamine and serotonin receptors. Additional clinical research is ongoing to evaluate its potential role in conditions involving agitation and hyperarousal. Besides its accepted indications, BYSANTI is also undergoing a clinical trial as a once-daily adjunctive therapy in treatment-resistant major depressive disorder in a continuing clinical trial that is anticipated to conclude later this year.
Vanda Pharmaceuticals has indicated that BYSANTI is expected to become commercially available in the third quarter of 2026. The company expects that regulatory data exclusivity and U.S. patents protections extending to 2044. The approval follows the company’s December 2025 approval of NEREUS, representing its second new drug approval within two months.
Bipolar I disorder accounts for a significant proportion of the approximately 10 million Americans living with bipolar disorder. It is characterized by manic or mixed episodes that require effective symptom management to improve clinical outcomes. Schizophrenia affects an estimated 2.8 million adults in the United States (approximately 1% of the population) and is associated with significant functional impairment and reduced quality of life.
BYSANTI carries a boxed warning for increased mortality in elderly adults with psychosis related to dementia and is not approved for use in that population.
Additional warnings and precautions include cerebral vascular adverse reactions among the elderly patients with dementia related psychosis, QTc prolongation that can result in torsade de pointes and sudden death, neuroleptic malignant syndrome, tardive dyskinesia, metabolic alterations, orthostatic hypotension, seizures, hematologic abnormalities, and hyperprolactinemia.
In the trials of schizophrenia, common adverse reactions (occurring in at least 5% of patients and at twice the placebo rate) included dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, and weight gain. Bipolar mania trials reported adverse reactions like tachycardia, dizziness, dry mouth, hepatic enzymes, nasal congestion, weight gain, and hypotension.
Reference: Vanda Pharmaceuticals. Vanda Pharmaceuticals Announces FDA Approval of BYSANTI™ (milsaperidone) for the treatment of Bipolar I Disorder and Schizophrenia – A New Chemical Entity Opening New Horizons in Psychiatric Innovation. Published February 20, 2026. Accessed February 25, 2026. Vanda Pharmaceuticals Announces FDA Approval of BYSANTI™ (milsaperidone) for the treatment of Bipolar I Disorder and Schizophrenia – A New Chemical Entity Opening New Horizons in Psychiatric Innovation
