Bysanti (milsaperidone): FDA approval, pivotal trial and safety
Approved
Type
New molecular entity · Oral
FDA-approved use
To treat schizophrenia and to treat manic or mixed episodes associated with bipolar I disorderWording from FDA's list of novel approvals.
FDA review
Standard review
Company
Vanda
Application
NDA 220358
Specialty
Psychiatry
Boxed warning: Increased mortality in elderly patients with dementia-related psychosis
At a glance
Bysanti (milsaperidone) is an atypical antipsychotic approved in February 2026 for adults with schizophrenia and for acute manic or mixed episodes of bipolar I disorder. Approval rests on efficacy studies of iloperidone, which interconverts with milsaperidone in the body. In those trials iloperidone beat placebo on the primary symptom scales. The boxed warning is increased mortality in elderly patients with dementia-related psychosis.
What it is and how it works
The mechanism is unknown. Efficacy may come from a mix of dopamine type 2 and serotonin type 2 antagonism, as with other atypical antipsychotics. Milsaperidone and iloperidone rapidly interconvert in vivo, and milsaperidone has a receptor binding profile similar to iloperidone. Bysanti is therefore a close relative of an existing antipsychotic, not a new mechanism.
Pivotal trials
Study 1 (iloperidone, schizophrenia)
Design
Six-week randomized, placebo- and active-controlled trial with two flexible dose ranges of iloperidone.
Patients
706 adults with schizophrenia.
Compared with
Placebo and risperidone.
Primary endpoint
Change from baseline in BPRS total score at day 42.
Result
Both iloperidone dose ranges were superior to placebo. Effect sizes are not given in the sources. Risperidone appeared better in the first 2 weeks, possibly because of faster titration. Among patients treated at least 2 weeks, efficacy looked comparable.
How does Bysanti (milsaperidone) compare with the alternatives (Risperidone, Ziprasidone, Olanzapine) for schizophrenia and to treat manic or mixed episodes associated with bipolar I disorder? Summarize head-to-head and indirect evidence, efficacy, safety and where each fits, with citations.
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Study 2 (iloperidone, schizophrenia; genetic signature analysis) NCT00254202
Design
Four-week inpatient randomized, double-blind, placebo- and ziprasidone-controlled trial with a fixed iloperidone dose. The publication is a pharmacogenetic analysis of this study.
Patients
604 adults with schizophrenia in the trial per the label; 409 patients of various ethnic origins in the genetic analysis.
Compared with
Placebo and ziprasidone.
Primary endpoint
Change from baseline in PANSS total score at day 28.
Result
Iloperidone was superior to placebo on PANSS total score per the label, with similar efficacy to ziprasidone. Effect size is not given in the sources. In the genetic analysis, more than 75% of iloperidone-treated patients with the optimal genotype combinations had at least 20% improvement, versus 37% with other genotypes.
Other results
Patients with favorable genotypes responded by the first week. The genotype link was not seen with ziprasidone.
The boxed warning covers increased risk of death in elderly patients with dementia-related psychosis; the drug is not approved for that use. Warnings include cerebrovascular events in that population, QTc prolongation with risk of torsade de pointes, neuroleptic malignant syndrome, tardive dyskinesia, metabolic changes, orthostatic hypotension and syncope, seizures, and leukopenia, neutropenia and agranulocytosis. Avoid combining it with other QTc-prolonging drugs, and monitor potassium and magnesium in patients at risk. Common adverse reactions in schizophrenia were dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia and weight gain. In bipolar mania, increased hepatic enzymes and hypotension were also common.
What it competes with
Schizophrenia and bipolar I mania are treated mainly with antipsychotics, and mood stabilizers are used in mania. Choice depends on side-effect profile, comorbidities and prior response.
RisperidoneEstablished atypical antipsychotic for schizophrenia and bipolar mania; may be started with faster titration.
ZiprasidoneAtypical antipsychotic that also needs gradual titration; QTc effects are a consideration.
OlanzapineEffective atypical antipsychotic, with notable metabolic effects.
AripiprazolePartial agonist antipsychotic often chosen for lower metabolic burden.
LithiumMood stabilizer used for acute mania in bipolar I disorder; needs level monitoring.
Bottom line for clinicians
Bysanti is an option for adults with schizophrenia or acute bipolar I mania who need an atypical antipsychotic. Its evidence comes from iloperidone studies, not from trials of milsaperidone itself. Weigh QTc risk, orthostasis, metabolic effects and the need for slow titration against alternatives.
Dosing, contraindications and full warnings are in the prescribing information.
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Last updated October 28, 2026 by 2 Minute Medicine.
For healthcare professionals. A summary of public FDA documents and published trials, not medical advice. Check the full prescribing information before prescribing.
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