FDA批准Cobenfy(KarXT)，一种首创的毒蕈碱激动剂，用于治疗成人精神分裂症

Author: Medicalhalo

Release time: 2025-10-19 11:44:20

On September 26, 2024, Bristol-Myers Squibb announced that the U.S. Food and Drug Administration (FDA) has approved Cobenfy (KarXT), an oral drug for the treatment of schizophrenia in adults. Cobenfy (KarXT) represents the first new drug class in decades and introduces an entirely new approach to treating schizophrenia by selectively targeting M1 and M4 receptors in the brain without blocking D2 receptors.

Chris Boerner, Chairman and CEO of Bristol-Myers Squibb "Today's landmark approval of our first-in-class schizophrenia treatment is an important milestone for the patient community - after more than 30 years, there is now a new pharmacological approach to schizophrenia, one that has the potential to change the treatment paradigm," said Dr. It is estimated to affect approximately 2.8 million people in the United States. Symptoms often first appear in early adulthood and appear differently in each person, making them difficult to diagnose and manage. Although the current standard of care can effectively control the symptoms of schizophrenia, up to 60% of patients experience insufficient symptom improvement during treatment or experience intolerable side effects.

"For people with schizophrenia, finding a treatment that's right for them is often difficult. Having multiple treatment options gives patients and healthcare providers the tools to help manage this serious illness," said Gordon Lavigne, CEO of the Schizophrenia and Psychosis Action Alliance. "People with schizophrenia crave and deserve more. Today's approval provides a new option that allows people with schizophrenia to move forward and rebuild their lives with appropriate support."

The safety and tolerability profile of Cobenfy (KarXT) has been confirmed in short- and long-term trials. In the Phase 3 EMERGENT-2 and EMERGENT-3 trials, the most common adverse reactions (incidence ≥5% and at least twice the rate in the placebo group) were nausea, dyspepsia, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, dizziness, and gastroesophageal reflux disease. Cobenfy (KarXT) does not have the warnings and precautions of the atypical antipsychotic class and does not have a boxed warning.

"Due to its heterogeneous nature, schizophrenia is not a 'one-size-fits-all' disease, and patients are often stuck in a cycle of discontinuing and switching medications," said Rishi Kakar, MD, chief academic officer and medical director of Segal Trials and an investigator on the EMERGENT program. "The approval of Cobenfy (KarXT) is a transformative moment for the treatment of schizophrenia because historically, drugs approved to treat schizophrenia have relied on the same major pathways in the brain. By harnessing a novel pathway, Cobenfy (KarXT) provides new options for managing this challenging disease."

About Schizophrenia

Schizophrenia is a persistent and often disabling psychiatric disorder that affects a person's thinking, feelings and behavior. Schizophrenia has three symptom domains, including positive symptoms (e.g., hallucinations, delusions, disorganized thinking and speech), negative symptoms (e.g., lack of motivation, lack of emotional expressiveness/apathy, social withdrawal), and cognitive dysfunction (e.g., impaired attention, memory, attention, and decision-making deficits).

The symptoms of schizophrenia can affect all aspects of people's lives, making it difficult to maintain employment, live independently, and manage relationships. Schizophrenia affects nearly 24 million people worldwide, including 2.8 million in the United States, and is one of the top 15 causes of disability worldwide.

About Cobenfy(KarXT)

Cobenfy, formerly known as KarXT, is an oral drug used to treat schizophrenia in adults. Cobenfy (KarXT) combines xanomeline, a dual M1- and M4-biased muscarinic receptor agonist, with trospium chloride, a muscarinic receptor antagonist that does not significantly cross the blood-brain barrier and acts primarily in peripheral tissues. Although the exact mechanism of action of Cobenfy (KarXT) is unknown, its efficacy is thought to be due to xanomelline's agonist activity at the M1 and M4 muscarinic acetylcholine receptors in the central nervous system.

Indications for Cobenfy (KarXT)

Cobenfy (KarXT) is suitable for the treatment of schizophrenia in adults.

Contraindications

Cobenfy (KarXT) is contraindicated in the following patients:

Urinary retention.

Moderate (Child-Pugh class B) or severe (Child-Pugh class C) liver dysfunction.

Gastric retention.

Have a history of allergy to Cobenfy (KarXT), and angioedema has been reported when using Cobenfy (KarXT).

Untreated angle-closure glaucoma.

Cobenfy (KarXT) Warnings and Precautions

Risk of Urinary Retention: Cobenfy (KarXT) can cause urinary retention. Elderly patients and patients with clinically significant bladder outlet obstruction and incomplete bladder emptying (e.g., patients with benign prostatic hyperplasia, diabetic cystopathy) may be at increased risk for developing urinary retention. Cobenfy (KarXT) is contraindicated in patients with pre-existing urinary retention and is not recommended in patients with moderate or severe renal impairment.

Risk of use in patients with hepatic impairment: Compared with patients with normal liver function, patients with hepatic impairment have higher systemic exposure to xanomelline, one of the components of Cobenfy (KarXT), which may lead to an increased incidence of Cobenfy (KarXT)-related adverse reactions. Cobenfy (KarXT) is contraindicated in patients with moderate or severe hepatic impairment. Cobenfy (KarXT) is not recommended for use in patients with mild hepatic impairment. Assess liver enzymes before initiating treatment with Cobenfy (KarXT) and as clinically necessary during treatment.

Risk of use in patients with biliary tract disease: When symptoms such as indigestion, nausea, vomiting or epigastric pain occur, gallbladder disease, biliary tract disease and pancreatitis should be evaluated according to clinical indications. Cobenfy (KarXT) should be discontinued if signs or symptoms of overt liver injury occur, such as jaundice, pruritus, or alanine aminotransferase levels greater than five times the upper limit of normal or five times the baseline value.

Reduced gastrointestinal motility: Cobenfy (KarXT) should be administered with caution to patients with gastrointestinal obstructive disease due to the risk of gastric retention. Cobenfy (KarXT) should be used with caution in patients with conditions such as ulcerative colitis, intestinal atony, and myasthenia gravis.

Risk of angioedema: Angioedema of the face, lips, tongue and/or throat has been reported with use of Cobenfy (KarXT) and its component trospium chloride. If the tongue, hypopharynx, or larynx is involved, Cobenfy (KarXT) should be discontinued and appropriate treatment initiated and/or necessary measures taken to ensure a patent airway. Cobenfy (KarXT) is contraindicated in patients with a history of allergy to trospium chloride.

Cobenfy (KarXT) Adverse Reactions

The most common adverse reactions (≥5% and at least twice the rate in the placebo group): nausea, dyspepsia, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, dizziness and gastroesophageal reflux disease.