The FDA has approved Cobenfy (xanomeline and trospium chloride) for the treatment of schizophrenia in adults, representing the first new class of drug for this condition in over three decades. This oral agent offers a novel approach by targeting M1 and M4 muscarinic receptors, differing from traditional antipsychotics that primarily affect dopaminergic and serotonergic pathways. The approval provides a new alternative for patients who may not respond to or tolerate dopamine-blocking agents. Tiffany Farchione, MD, of the FDA's Center for Drug Evaluation and Research, stated that this drug takes the first new approach to schizophrenia treatment in decades, offering a new option for managing this challenging condition.
Efficacy and Safety Data
The approval of Cobenfy was supported by data from the EMERGENT clinical program, including the EMERGENT-2 and EMERGENT-3 trials. These 5-week trials demonstrated statistically significant reductions in the Positive and Negative Syndrome Scale (PANSS) total score compared to placebo (P < 0.0001 for both):
- EMERGENT-2: -21.2 vs -11.6, respectively
- EMERGENT-3: -20.6 vs -12.2, respectively
Key secondary endpoints were also met in EMERGENT-2. Rishi Kakar, MD, of Segal Trials, highlighted that Cobenfy offers a new option by leveraging a novel pathway, addressing the heterogeneous nature of schizophrenia.
Side Effects and Contraindications
The most common side effects of xanomeline-trospium chloride (in ≥5% of patients and at least twice placebo) included nausea, dyspepsia, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, dizziness, and gastrointestinal reflux disease. The combination was not associated with side effects typically common of other schizophrenia agents, such as weight gain, somnolence, and extrapyramidal symptoms. Contraindications include urinary retention, moderate or severe hepatic impairment, gastric retention, a history of hypersensitivity to the ingredients, or untreated narrow-angle glaucoma. Warnings address angioedema, central nervous system effects, increased heart rate, and use in patients with biliary disease. It is not recommended in patients with moderate to severe renal impairment (eGFR <60 mL/min/1.73 m2).
Dosing and Availability
Xanomeline-trospium is available in 50 mg/20 mg, 100 mg/20 mg, and 125 mg/30 mg capsules. Bristol Myers Squibb anticipates launching the drug in late October, with an expected list price of $1,850 per month or approximately $22,500 annually before rebates or discounts.
Market Impact and Analyst Projections
Analysts project that Cobenfy could reach peak sales of $2.4 billion for schizophrenia and an additional $3.9 billion for Alzheimer's psychosis. BMO Capital adjusted its price target on Bristol-Myers Squibb shares to $53.00, while Goldman Sachs reaffirmed a Buy rating with a price target of $57.00. The FDA approval also triggers $29 million in payments to PureTech, the original developer of the drug, with potential future royalties on net annual sales over $2 billion.
