Evicenter
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LB-102

Schizophrenia

Regulatory submission
Not announced
Launch
Not announced
Last updated
345 sources

Product information and disease descriptionPlace of product in therapyApproaches to treatmentCurrent treatment options and standard of care

Muscarinic receptor agonists

10 evidence topics · 10 sources

FDA approval of xanomeline and trospium chloride

“It is the first antipsychotic drug approved to treat schizophrenia that targets cholinergic receptors as opposed to dopamine receptors, which has long been the standard of care.” (opens the source at this quote in a new tab)

“The prescribing information includes warnings that Cobenfy can cause urinary retention, increased heart rate, decreased gastric movement or angioedema (swelling beneath the skin) of the face and lips.” (opens the source at this quote in a new tab)

Xanomeline and trospium chloride: indication and dosing

“COBENFY is a combination of xanomeline, a muscarinic agonist, and trospium chloride, a muscarinic antagonist, indicated for the treatment of schizophrenia in adults.” (opens the source at this quote in a new tab)

“Recommended starting dosage of COBENFY is 50 mg/20 mg orally twice daily for at least two days, then increase the dosage to 100 mg/20 mg twice daily for at least five days.” (opens the source at this quote in a new tab)

Xanomeline and trospium chloride: warnings and precautions

“Risk of Urinary Retention: COBENFY can cause urinary retention.” (opens the source at this quote in a new tab)

“Risk of Use in Patients with Hepatic Impairment: COBENFY is contraindicated in patients with moderate to severe hepatic impairment and is not recommended in patients with mild hepatic impairment.” (opens the source at this quote in a new tab)

“Risk of Use in Patients with Biliary Disease: Assess liver enzymes and bilirubin prior to initiating COBENFY and as clinically indicated.” (opens the source at this quote in a new tab)

Xanomeline and trospium chloride: adverse reactions in the pooled 5-week trials

“The adverse reaction findings are based on two pooled 5-week, placebo-controlled, flexible-dose studies in 504 adult patients with schizophrenia” (opens the source at this quote in a new tab)

“The most common side effects of Cobenfy are nausea, indigestion, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia (increased heartbeat), dizziness and gastroesophageal reflux disease.” (opens the source at this quote in a new tab)

EMERGENT-2: primary endpoint and tolerability

“EMERGENT-2 was a randomised, double-blind, placebo-controlled, flexible-dose, 5-week, inpatient, phase 3 trial in people with schizophrenia.” (opens the source at this quote in a new tab)

“The trial met the primary endpoint with a mean change from baseline to week 5 in PANSS total score that favoured KarXT (-21·2 points, SE 1·7) versus placebo (-11·6 points, 1·6; least squares mean difference -9·6; 95% CI -13·9 to -5·2; p<0·0001, Cohen's d effect size=0·61).” (opens the source at this quote in a new tab)

“Treatment-emergent adverse event rates of extrapyramidal motor symptoms (KarXT, zero [0%] vs placebo, zero [0%]), akathisia (one [1%] vs one [1%]), weight gain (zero [0%] vs one [1%]), and somnolence (six [5%] vs five [4%]) were similar between the KarXT and placebo groups, as were adverse event-related discontinuation rates (nine [7%] vs seven [6%]).” (opens the source at this quote in a new tab)

EMERGENT-3: primary endpoint and tolerability

“At week 5, xanomeline-trospium significantly reduced PANSS total score compared with placebo (xanomeline-trospium , −20.6; placebo, −12.2; least squares mean difference, −8.4; 95% CI, −12.4 to −4.3; P < .001; Cohen d effect size, 0.60).” (opens the source at this quote in a new tab)

“The most common TEAEs in the xanomeline-trospium vs placebo group were nausea (24 participants [19.2%] vs 2 participants [1.6%]), dyspepsia (20 participants [16.0%] vs 2 participants [1.6%]), vomiting (20 participants [16.0%] vs 1 participant [0.8%]), and constipation (16 participants [12.8%] vs 5 participants [3.9%]).” (opens the source at this quote in a new tab)

ARISE: adjunctive xanomeline and trospium chloride with an atypical antipsychotic

“In the Phase 3 trial, adjunctive Cobenfy treatment demonstrated a 2.0-point reduction in the Positive and Negative Syndrome Scale (PANSS) total score compared to placebo with an atypical antipsychotic at Week 6, which did not reach the threshold for statistical significance for the primary endpoint (P = 0.11).” (opens the source at this quote in a new tab)

“In a post-hoc subgroup analysis there was a notable difference in response between subjects treated with risperidone as a background therapy compared with the remaining subjects treated with other background antipsychotics (non-risperidone).” (opens the source at this quote in a new tab)

Emraclidine: phase 1b and phase 2 EMPOWER results

“These data support further investigation of emraclidine as a once-daily treatment for schizophrenia without need for titration and with a potentially favourable side-effect profile.” (opens the source at this quote in a new tab)

“EMPOWER-1 and EMPOWER-2 Phase 2 clinical trials did not meet their primary endpoint” (opens the source at this quote in a new tab)

“In the EMPOWER trials, emraclidine was well-tolerated with a safety profile comparable to that observed in the Phase 1b trial.” (opens the source at this quote in a new tab)

Consensus panel report on clinical use of xanomeline and trospium chloride

“In July 2025, a consensus panel of clinicians with expertise in treating schizophrenia and real-world experience using XT convened to discuss practical strategies for its use across treatment settings.” (opens the source at this quote in a new tab)

“The panel concluded that XT should be considered early in the course of illness, particularly in first-episode psychosis, because it may alter long-term outcomes while reducing reliance on high-dose dopamine antagonists.” (opens the source at this quote in a new tab)

NICE technology appraisal of xanomeline tartrate and trospium chloride: status

“Expected publication date: 14 July 2027” (opens the source at this quote in a new tab)

“Status: In progress” (opens the source at this quote in a new tab)

Recommendations on muscarinic receptor agonists in the APA, VA/DoD, NICE, and Australian and New Zealand guidelines

No evidence found.