FDA批准Cobenfy(KarXT)，一种治疗精神分裂症的新型药物

Friday, September 27, 2024 The U.S. Food and Drug Administration on Thursday approved the first new drug in decades to help fight schizophrenia.

Cobenfy (KarXT) (xanomeline/trospium) could give patients what they have long wanted: a way to relieve the hallucinations and "auditory hallucinations" that disrupt their lives without the weight gain and unresponsive side effects of current dopamine-focused drugs.

Cobenfy (KarXT) does affect dopamine, but it does so indirectly through so-called cholinergic receptors, thereby altering the activity of another neurotransmitter, acetylcholine.

"Schizophrenia is one of the leading causes of disability worldwide. It is a severe, chronic mental illness that often impairs patients' quality of life," said Tiffany Farchione, Ph.D., director of the Division of Psychiatry in the Office of Neuroscience in the FDA's Center for Drug Evaluation and Research.

"This drug uses an entirely new approach to treating schizophrenia that has been available for decades," she said in an FDA press release. "This approval provides a new alternative to antipsychotic medications previously taken by people with schizophrenia."

According to the FDA, about 1 percent of people suffer from schizophrenia, which is characterized by intrusive thoughts, hallucinations (including auditory hallucinations) and paranoia that can significantly interfere with daily life and social interactions. The agency said it can be a debilitating disease and significantly increases the risk of death at a young age. The FDA notes that nearly 5% of people with schizophrenia die by suicide.

Nearly all existing schizophrenia drugs control symptoms by blocking dopamine receptors in brain cells. This can keep symptoms under control, but for decades, users have complained of side effects such as weight gain, lack of motivation and slowed reflexes, and discontinuation is common.

Cobenfy (KarXT) is produced by Bristol-Myers Squibb Company. The drug was tested in two five-week "double-blind" trials: neither patients nor those dispensing the drug knew whether patients received Cobenfy (KarXT) or a placebo. Patient outcomes were assessed using a standard 30-item scale measuring schizophrenia symptoms. "In both studies, participants who received Cobenfy (KarXT) experienced meaningful symptom reductions from baseline to week 5," the FDA said.

Possible side effects

The most obvious are gastrointestinal reactions, such as nausea, indigestion, constipation and vomiting. A rapid heart rate and acid reflux may also occur. Due to the risk of liver damage, Cobenfy (KarXT) is not recommended for people with existing liver damage.

Bristol-Myers Squibb noted in a company press release that unlike other antipsychotics used to treat schizophrenia, Cobenfy (KarXT) "does not have the warnings and precautions associated with the atypical antipsychotic class and does not have the [FDA-required] black box warning on its label."

Both trials only lasted 5 weeks, so their long-term effectiveness and safety are unknown. "We don't know how effective it will be after five weeks," said Dr. David Rind, medical director of the Institute for Clinical and Economic Review, which tracks newly approved drugs. Rind told the New York Times that people are "a little bit skeptical of claims until you actually see the effects of the drug." He expressed doubts about Cobenfy's (KarXT) potential long-term effectiveness or neurological effects such as movement disorders.