Key TakeawaysThe FDA has approved Cobenfy, the first new schizophrenia treatment in over 30 years.Cobenfy helps reduce both positive and negative schizophrenia symptoms, with side effects compared to current medications.Clinical trials for Cobenfy showed no significant weight gain or treatment discontinuation, but long-term effectiveness remains uncertain due to short study durations.The Food and Drug Administration (FDA) last week approved Bristol Myers Squibb’s antipsychotic drug Cobenfy (xanomeline and trospium chloride), the firstschizophreniatreatment with an entirely new mechanism of action in over 70 years.Current antipsychotic medications block dopamine receptors to help manage hallucinations, delusions, and other symptoms of schizophrenia. But those drugs can cause serious motor and metabolic side effects, like involuntary movements and weight gain, that can lead to heart disease and diabetes.Cobenfy targets a different neurotransmitter to indirectly influence dopamine levels. Previously called KarXT, Cobenfy is taken twice daily as a pill.In the United States, an estimated 2.6 million people have ever been treated forschizophrenia spectrum disorders(which include schizoaffective disorder and schizophreniform disorder).Treatments includecognitive behavioral therapy (CBT), community support, andantipsychotic medications.Among people using antipsychotic medications, more than a third may discontinue their medications, and more than 10% discontinue medication because it isn’t effective for them.“Schizophrenia is not a one-size-fits-all condition, and people often find themselves in a cycle of discontinuing and switching therapies,” Rishi Kakar, MD, chief scientific officer and medical director at Segal Trials and investigator for the Cobenfy clinical trials, said in a statement. “Historically, medicines approved to treat schizophrenia have relied on the same primary pathways in the brain. By leveraging a novel pathway, Cobenfy offers a new option to manage this challenging condition.”Early Signs and Symptoms of SchizophreniaHow Does Cobenfy Work?Cobenfy combines xanomeline, an experimental drug for Alzheimer’s disease, with trospium, which helps to suppress side effects.Unlike current antipsychotic medications, xanomeline doesn’t bind directly to dopamine receptors. It instead targets the M1 and M4 muscarinic receptors in the central nervous system.When xanomeline was first developed, it showed antipsychotic effects but also caused “unbearable side effects,” saidXiaoduo Fan, MD, MPH, professor of psychiatry and psychopharmacology at the University of Massachusetts T. H. Chan School of Medicine.Adding trospium keeps xanomeline from crossing the blood-brain barrier and activating receptors that can cause people to feel nausea, constipation, and other gastrointestinal distress.“Overall, those side effects are much more mild than many years ago when we used xanomeline alone. It’s now tolerable to a patient,” Fan said.Existing antipsychotics can generally manage “positive” symptoms of schizophrenia, such as depression, hallucinations, and delusions, but are much less effective at reducing “negative” symptoms like social withdrawal and lack of interest in life. In clinical trials, Cobenfy was shown to minimize both positive and negative symptoms. It also appeared to improve cognitive outcomes, Fan noted.There was no difference in weight gain or treatment discontinuation between Cobenfy and a placebo.Currently, the drug clozapine is the only option for treatment-resistant schizophrenia. However, up to 60% of patients don’t respond to it, and it is linked to metabolic issues.Fan said Cobenfy could be considered before using clozapine for treatment-resistant patients. It could also benefit patients who have developed significant side effects associated with long-term use of other antipsychotic medications, such as involuntary movement, uncontrollable diabetes, or cardiovascular disease.The FDA approved Cobenfy without a boxed warning—the agency’s strongest alert for serious adverse events, which usually accompanies antipsychotics. However, the agency noted that Cobenfy should not be prescribed to patients with urinary retention, moderate or severe kidney or liver disease, gastric retention, or untreated narrow-angle glaucoma.Positive and Negative Schizophrenia SymptomsHow Well Does Cobenfy Work in the Long Run?There are just three published placebo-controlled studies, each lasting only five weeks. Some analysts say the short duration of clinical trials leaves questions about the drug’s long-term efficacy.In a report earlier this year, The Institute for Clinical and Economic Review wrote that “the major source of uncertainty is the lack of data on the efficacy of [Cobenfy] for longer than five weeks.” The authors said that given the lack of long-term data and because Cobenfy is a new type of antipsychotic, it’s hard to judge whether the drug is superior to other available options.In April, BMS shared topline results from two open-label trials that lasted up to a year. The company said participants in those trials didn’t have any serious metabolic side effects or develop motor problems.“This is a very promising medication in many ways,” Fan said. “Whether or not this is going to be a game changer, meaning it’s going to be significantly better than currently available medications, I think we still need a lot more data to see how it works in the real world.”BMS said Cobenfy will be available in October at a list price of $1,850 per month before insurance and rebates. The company said that the price is in line with other antipsychotic schizophrenia medications.The company is investigating whether Cobenfy could be used to treat Alzheimer’s disease psychosis, a condition for which there are no treatments. It said the drug may also be useful as a treatment for Bipolar I disorder and Alzheimer’s disease agitation.Medications to Treat SchizophreniaWhat This Means For YouCobenfy offers a new option for managing schizophrenia, especially for patients who have not responded well to traditional treatments or have experienced severe side effects. Talk to your healthcare provider to see if this medication might be appropriate for your situation.

Key TakeawaysThe FDA has approved Cobenfy, the first new schizophrenia treatment in over 30 years.Cobenfy helps reduce both positive and negative schizophrenia symptoms, with side effects compared to current medications.Clinical trials for Cobenfy showed no significant weight gain or treatment discontinuation, but long-term effectiveness remains uncertain due to short study durations.

Key Takeaways

The FDA has approved Cobenfy, the first new schizophrenia treatment in over 30 years.Cobenfy helps reduce both positive and negative schizophrenia symptoms, with side effects compared to current medications.Clinical trials for Cobenfy showed no significant weight gain or treatment discontinuation, but long-term effectiveness remains uncertain due to short study durations.

The Food and Drug Administration (FDA) last week approved Bristol Myers Squibb’s antipsychotic drug Cobenfy (xanomeline and trospium chloride), the firstschizophreniatreatment with an entirely new mechanism of action in over 70 years.

Current antipsychotic medications block dopamine receptors to help manage hallucinations, delusions, and other symptoms of schizophrenia. But those drugs can cause serious motor and metabolic side effects, like involuntary movements and weight gain, that can lead to heart disease and diabetes.

Cobenfy targets a different neurotransmitter to indirectly influence dopamine levels. Previously called KarXT, Cobenfy is taken twice daily as a pill.

In the United States, an estimated 2.6 million people have ever been treated forschizophrenia spectrum disorders(which include schizoaffective disorder and schizophreniform disorder).Treatments includecognitive behavioral therapy (CBT), community support, andantipsychotic medications.Among people using antipsychotic medications, more than a third may discontinue their medications, and more than 10% discontinue medication because it isn’t effective for them.

“Schizophrenia is not a one-size-fits-all condition, and people often find themselves in a cycle of discontinuing and switching therapies,” Rishi Kakar, MD, chief scientific officer and medical director at Segal Trials and investigator for the Cobenfy clinical trials, said in a statement. “Historically, medicines approved to treat schizophrenia have relied on the same primary pathways in the brain. By leveraging a novel pathway, Cobenfy offers a new option to manage this challenging condition.”

Early Signs and Symptoms of Schizophrenia

How Does Cobenfy Work?

Cobenfy combines xanomeline, an experimental drug for Alzheimer’s disease, with trospium, which helps to suppress side effects.

Unlike current antipsychotic medications, xanomeline doesn’t bind directly to dopamine receptors. It instead targets the M1 and M4 muscarinic receptors in the central nervous system.

When xanomeline was first developed, it showed antipsychotic effects but also caused “unbearable side effects,” saidXiaoduo Fan, MD, MPH, professor of psychiatry and psychopharmacology at the University of Massachusetts T. H. Chan School of Medicine.

Adding trospium keeps xanomeline from crossing the blood-brain barrier and activating receptors that can cause people to feel nausea, constipation, and other gastrointestinal distress.

“Overall, those side effects are much more mild than many years ago when we used xanomeline alone. It’s now tolerable to a patient,” Fan said.

Existing antipsychotics can generally manage “positive” symptoms of schizophrenia, such as depression, hallucinations, and delusions, but are much less effective at reducing “negative” symptoms like social withdrawal and lack of interest in life. In clinical trials, Cobenfy was shown to minimize both positive and negative symptoms. It also appeared to improve cognitive outcomes, Fan noted.

There was no difference in weight gain or treatment discontinuation between Cobenfy and a placebo.

Currently, the drug clozapine is the only option for treatment-resistant schizophrenia. However, up to 60% of patients don’t respond to it, and it is linked to metabolic issues.

Fan said Cobenfy could be considered before using clozapine for treatment-resistant patients. It could also benefit patients who have developed significant side effects associated with long-term use of other antipsychotic medications, such as involuntary movement, uncontrollable diabetes, or cardiovascular disease.

The FDA approved Cobenfy without a boxed warning—the agency’s strongest alert for serious adverse events, which usually accompanies antipsychotics. However, the agency noted that Cobenfy should not be prescribed to patients with urinary retention, moderate or severe kidney or liver disease, gastric retention, or untreated narrow-angle glaucoma.

Positive and Negative Schizophrenia Symptoms

How Well Does Cobenfy Work in the Long Run?

There are just three published placebo-controlled studies, each lasting only five weeks. Some analysts say the short duration of clinical trials leaves questions about the drug’s long-term efficacy.

In a report earlier this year, The Institute for Clinical and Economic Review wrote that “the major source of uncertainty is the lack of data on the efficacy of [Cobenfy] for longer than five weeks.” The authors said that given the lack of long-term data and because Cobenfy is a new type of antipsychotic, it’s hard to judge whether the drug is superior to other available options.

In April, BMS shared topline results from two open-label trials that lasted up to a year. The company said participants in those trials didn’t have any serious metabolic side effects or develop motor problems.

“This is a very promising medication in many ways,” Fan said. “Whether or not this is going to be a game changer, meaning it’s going to be significantly better than currently available medications, I think we still need a lot more data to see how it works in the real world.”

BMS said Cobenfy will be available in October at a list price of $1,850 per month before insurance and rebates. The company said that the price is in line with other antipsychotic schizophrenia medications.

The company is investigating whether Cobenfy could be used to treat Alzheimer’s disease psychosis, a condition for which there are no treatments. It said the drug may also be useful as a treatment for Bipolar I disorder and Alzheimer’s disease agitation.

Medications to Treat Schizophrenia

What This Means For YouCobenfy offers a new option for managing schizophrenia, especially for patients who have not responded well to traditional treatments or have experienced severe side effects. Talk to your healthcare provider to see if this medication might be appropriate for your situation.

What This Means For You

Cobenfy offers a new option for managing schizophrenia, especially for patients who have not responded well to traditional treatments or have experienced severe side effects. Talk to your healthcare provider to see if this medication might be appropriate for your situation.

7 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Kingwell K.FDA approves first schizophrenia drug with new mechanism of action since 1950s.Nat Rev Drug Discov. Published online September 26, 2024. doi:10.1038/d41573-024-00155-8RTI International.Mental and substance use disorders prevalence study.Dixon LB, Goldman HH, Srihari VH, Kane JM.Transforming the treatment of schizophrenia in the United States: the RAISE initiative.Annu Rev Clin Psychol. 2018;14:237-258. doi:10.1146/annurev-clinpsy-050817-084934Keepers GA, Fochtmann LJ, Anzia JM, et al.The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia.Focus (Am Psychiatr Publ). 2020;18(4):493-497. doi:10.1176/appi.focus.18402Business Wire.U.S. Food and Drug Administration approves Bristol Myers Squibb’s (xanomeline and trospium chloride), a first-in-class muscarinic agonist for the treatment of schizophrenia in adults.The Lancet.Time for renewed optimism for schizophrenia?.Lancet. 2024;403(10422):117. doi:10.1016/S0140-6736(24)00047-3Institute for Clinical and Economic Review.KarXT for schizophrenia: effectiveness and value; evidence report.

7 Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Kingwell K.FDA approves first schizophrenia drug with new mechanism of action since 1950s.Nat Rev Drug Discov. Published online September 26, 2024. doi:10.1038/d41573-024-00155-8RTI International.Mental and substance use disorders prevalence study.Dixon LB, Goldman HH, Srihari VH, Kane JM.Transforming the treatment of schizophrenia in the United States: the RAISE initiative.Annu Rev Clin Psychol. 2018;14:237-258. doi:10.1146/annurev-clinpsy-050817-084934Keepers GA, Fochtmann LJ, Anzia JM, et al.The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia.Focus (Am Psychiatr Publ). 2020;18(4):493-497. doi:10.1176/appi.focus.18402Business Wire.U.S. Food and Drug Administration approves Bristol Myers Squibb’s (xanomeline and trospium chloride), a first-in-class muscarinic agonist for the treatment of schizophrenia in adults.The Lancet.Time for renewed optimism for schizophrenia?.Lancet. 2024;403(10422):117. doi:10.1016/S0140-6736(24)00047-3Institute for Clinical and Economic Review.KarXT for schizophrenia: effectiveness and value; evidence report.

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Kingwell K.FDA approves first schizophrenia drug with new mechanism of action since 1950s.Nat Rev Drug Discov. Published online September 26, 2024. doi:10.1038/d41573-024-00155-8RTI International.Mental and substance use disorders prevalence study.Dixon LB, Goldman HH, Srihari VH, Kane JM.Transforming the treatment of schizophrenia in the United States: the RAISE initiative.Annu Rev Clin Psychol. 2018;14:237-258. doi:10.1146/annurev-clinpsy-050817-084934Keepers GA, Fochtmann LJ, Anzia JM, et al.The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia.Focus (Am Psychiatr Publ). 2020;18(4):493-497. doi:10.1176/appi.focus.18402Business Wire.U.S. Food and Drug Administration approves Bristol Myers Squibb’s (xanomeline and trospium chloride), a first-in-class muscarinic agonist for the treatment of schizophrenia in adults.The Lancet.Time for renewed optimism for schizophrenia?.Lancet. 2024;403(10422):117. doi:10.1016/S0140-6736(24)00047-3Institute for Clinical and Economic Review.KarXT for schizophrenia: effectiveness and value; evidence report.

Kingwell K.FDA approves first schizophrenia drug with new mechanism of action since 1950s.Nat Rev Drug Discov. Published online September 26, 2024. doi:10.1038/d41573-024-00155-8

RTI International.Mental and substance use disorders prevalence study.

Dixon LB, Goldman HH, Srihari VH, Kane JM.Transforming the treatment of schizophrenia in the United States: the RAISE initiative.Annu Rev Clin Psychol. 2018;14:237-258. doi:10.1146/annurev-clinpsy-050817-084934

Keepers GA, Fochtmann LJ, Anzia JM, et al.The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia.Focus (Am Psychiatr Publ). 2020;18(4):493-497. doi:10.1176/appi.focus.18402

Business Wire.U.S. Food and Drug Administration approves Bristol Myers Squibb’s (xanomeline and trospium chloride), a first-in-class muscarinic agonist for the treatment of schizophrenia in adults.

The Lancet.Time for renewed optimism for schizophrenia?.Lancet. 2024;403(10422):117. doi:10.1016/S0140-6736(24)00047-3

Institute for Clinical and Economic Review.KarXT for schizophrenia: effectiveness and value; evidence report.

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