| Drug Name |
COBENFY™ (xanomeline and trospium) |
| Active Ingredient |
xanomeline and trospium |
| Date of Approval |
September 26, 2024 |
| Manufacturer |
Karuna Therapeutics, Inc. |
| Approval Pathways and Indications |
Approval Pathway: NDA
Indication: COBENFY™ is indicated for the treatment of schizophrenia in adults. |
| Therapeutic Class |
Schizophrenia Agent; a muscarinic agonist and antagonist |
| Formulation |
Capsules (xanomeline/trospium chloride): 50mg/20mg, 100mg/20mg, 125mg/30mg |
| MoA |
The mechanism of action of xanomeline in the treatment of schizophrenia is unclear; however, its efficacy is thought to be due to its agonist activity at M1 and M4 muscarinic acetylcholine receptors in the central nervous system. Trospium chloride is a muscarinic antagonist. Trospium chloride antagonizes the muscarinic receptors primarily in the peripheral tissues. |
| Dosing and Administration |
The recommended dosage of COBENFY™ begins with one 50 mg/20 mg capsule orally twice daily for at least two days, increasing to a 100 mg/20 mg capsule twice daily for at least five days. Based on tolerability, it can be increased to a maximum of one 125 mg/30 mg capsule twice daily. Capsules must be taken at least one hour before or two hours after meals, and should not be opened. For geriatric patients, it is recommended to start with a 50 mg/20 mg capsule twice daily, with a slower titration if needed, and a maximum dosage of a 100 mg/20 mg capsule twice daily. |
| Administered by self or by HCP |
Administered by Self |
| Place in Therapy |
Schizophrenia is a leading cause of disability worldwide. It is a severe, chronic mental illness that is often damaging to a person’s quality of life. COBENFY™ represents the first new class of medicine in several decades and introduces a fundamentally new approach to treating schizophrenia by selectively targeting M1 and M4 receptors in the brain without blocking D2 receptors, which has long been the standard of care. With 40% of patients with schizophrenia not responding to current treatment and up to 60% experiencing a partial/inadequate response or intolerable adverse events during therapy, this new approval may offer new options to manage this condition.
COBENFY™ does not have atypical antipsychotic class warnings and precautions and does not have a boxed warning, but COBENFY™ can cause urinary retention, increased heart rate, decreased gastric movement, or angioedema of the face and lips. It is not recommended for patients with mild to severe hepatic impairment, moderate to severe renal impairment, or those with a history of hypersensitivity to its components. Patients should stop use if they experience signs of substantial liver disease. COBENFY™ should not be prescribed to patients with urinary or gastric retention, untreated narrow-angle glaucoma, or moderate to severe kidney or liver disease. Common side effects include nausea, indigestion, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, dizziness, and gastroesophageal reflux disease. |
| Expected Market Launch Date |
Late October |
| New Molecular Entity (NME) or Existing Formulation |
New Molecular Entity |
| Expected Cost |
$22,500 annually |
| Product Discontinuation |
N/A |
| Clinical Trials |
The FDA approval of COBENFY™ is supported by data from the EMERGENT clinical program, which includes three placebo-controlled efficacy and safety trials and two open-label trials evaluating the long-term safety and tolerability of COBENFY™ for up to one year. In the Phase 3 EMERGENT-2 and EMERGENT-3 trials, COBENFY™ met its primary endpoint, demonstrating statistically significant reductions of schizophrenia symptoms compared to placebo, as measured by the Positive and Negative Syndrome Scale (PANSS) total score change from baseline to week five. COBENFY™ demonstrated a 9.6-point reduction (-21.2 COBENFY™ vs. -11.6 placebo, p<0.0001) and an 8.4-point reduction (-20.6 COBENFY™ vs. -12.2 placebo; p<0.0001) in PANSS total score compared to placebo at week five in EMERGENT-2 and EMERGENT-3, respectively. In EMERGENT-2, COBENFY™ demonstrated a statistically significant improvement in illness from baseline to week five, as measured by the Clinical Global Impression-Severity score, a secondary endpoint in the trial.
The safety and tolerability profile of COBENFY™ has been established across acute and long-term trials. In the Phase 3 EMERGENT-2 and EMERGENT-3 trials, the most common adverse reactions (≥5% and at least twice placebo) were nausea, dyspepsia, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, dizziness and gastroesophageal reflux disease. |
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COBENFY Drug Approval History. Drugs.com. https://www.drugs.com/history/cobenfy.html. Accessed September 27, 2024.
U.S. Food and Drug Administration Approves Bristol Myers Squibb's COBENFY (Xanomeline-Trospium Chloride), First-in-Class Muscarinic Agonist for Schizophrenia in Adults. Drugs.com. https://www.drugs.com/newdrugs/u-s
-food-administration-approves-
bristol-myers-squibb-s-cobenfy-
xanomeline-trospium-chloride-first-6373.html. Published January 15, 2024. Accessed September 27, 2024.
FDA Approves Drug With New Mechanism of Action for the Treatment of Schizophrenia. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/
fda-approves-drug-new-mechanism-action-treatment-schizophrenia. Published January 15, 2024. Accessed September 27, 2024.
U.S. Food and Drug Administration Approves Bristol Myers Squibb's COBENFY (Xanomeline and Trospium Chloride), a First-in-Class Muscarinic Agonist for the Treatment of Schizophrenia in Adults. Bristol Myers Squibb. https://news.bms.com/news/corporate-financial/2024/
U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-
COBENFY-xanomeline-and-trospium-chloride
-a-First-In-Class-Muscarinic-Agonist-for-the-Treatment-of-Schizophrenia-in-Adults/default.aspx. Published January 15, 2024. Accessed September 27, 2024.
COBENFY Product Fact Sheet. Business Wire. https://mms.businesswire.com/media/
20240925382351/en/2255710/1/Cobenfy_Product_fact_sheet_FINAL.pdf. Accessed September 27, 2024.
COBENFY Package Insert. Bristol Myers Squibb. https://packageinserts.bms.com/pi/pi_cobenfy.pdf. Accessed September 27, 2024.
FDA Approves the Oral Medication KarXT for Schizophrenia. Managed Healthcare Executive. https://www.managedhealthcareexecutive.com/view/fda-approves-the-oral-medication-karxt-for-schizophrenia. Published January 15, 2024. Accessed September 27, 2024. |