(Schizophrenia affects around 24 million people globally and is among the top 15 leading causes of disability. In the United States, it affects around 2.8 million people.
Schizophrenia is a mental health condition characterized by hallucinations, delusions, and disorganized behavior and speech. It impacts a person's thoughts, behavior, and feelings. Hallucinations are hearing or seeing things that are usually not visible to others. On the other hand, delusion is believing in something that isn’t true. Overall effects lead to distorted behavior, and the person appears to lose a sense of reality, which makes life extremely tough.
The causes of schizophrenia range from genetics to changes in brain structure to imbalances in neurotransmitters like dopamine and glutamate.
The common symptoms that can be encountered in a schizophrenic patient are hallucinations, delusions, disorganized speech, altered behavior, social withdrawal, trouble sleeping, and feeling depressed. In people with schizophrenia, the rate of suicidal thoughts and attempts is higher than in people without schizophrenia.
Treatment of schizophrenia includes
Managing symptoms with antipsychotics Eg: first generation: chlorpromazine, fluphenazine, and haloperidol; second generation: aripiprazole, clozapine, olanzapine, quetiapine, and risperidone.
Psychological and social treatment Eg: psychotherapy, social skills training, family therapy, and vocational rehabilitation.
For individuals who do not respond to drug therapy, electroconvulsive therapy can be considered.
The antipsychotics work by predominantly blocking dopamine receptors, and the major side effects include dry mouth, dizziness, blurred vision, and weight gain, which can lead to diabetes.
COBENFY:
Cobenfy is a combination of xanomeline and trospium chloride. Xanomeline is a muscarinic receptor agonist and has a dual action. It acts on both M1 and M4 muscarinic receptors. Trospium chloride is a muscarinic receptor antagonist that acts mainly on peripheral tissues. However, the exact mechanism of Cobenfy is unknown.
COBENFY (xanomeline and trospium chloride) is available as capsules. The available doses are 50 mg/20 mg, 100 mg/20 mg, and 125 mg/30 mg capsules.
EMERGENT CLINICAL PROGRAM:
A clinical trial was conducted to assess the safety, efficacy, and tolerability of Cobenfy. In phase 3, EMERGENT 2 and EMERGENT 3 trials were conducted for 5 weeks. For both trials, the comparison was done by administering cobenfy to one group and placebo to the other. The endpoints were compared using the Positive and Negative Syndrome Scale (PANSS). At the end of trials after 5 weeks, there was a significant reduction of 9.6- points in EMERGENT 2 and 8.4 points in EMERGENT 3 trials, which suggests that the schizophrenia symptoms reduced when cobenfy was given compared to placebo. Apart from this, at the end of the 5-week trial, the COBENFY also showed improvement in illness when measured by the Clinical Global Impression-Severity (CGI-S) score.
With the drug treatment, nausea, vomiting, dyspepsia, constipation, tachycardia, hypertension, dizziness, and gastroesophageal reflux disease were the most common adverse reactions seen.
The conditions in which the drug shouldn’t be prescribed are urinary retention, hepatic or renal disease, gastric retention, and glaucoma.
Overall, across the trials, the drug has shown its efficacy and established its safety and tolerability, which ensures that it can now be used efficiently for the treatment of schizophrenia.
With the data generated from the EMERGENT clinical trial and COBENFY establishing its safety, efficacy, and tolerability, the U.S. Food and Drug Administration (FDA) for the treatment of schizophrenia announced the approval of Bristol Myers Squibb’s COBENFY (xanomeline and trospium chloride) which in the form of oral capsules is a novel treatment option that acts on M1 and M4 receptors without blocking D2 receptors, marking the first new class of therapy for the treatment of schizophrenia.
According to an article, Rishi Kakar, MD, chief scientific officer and medical director at Segal Trials and investigator in the EMERGENT program, was quoted as saying the following concerning the COBENFY for schizophrenia.
Due to its heterogeneous nature, schizophrenia is not a one-size-fits-all condition, and people often find themselves in a cycle of discontinuing and switching therapies. The approval of COBENFY is a transformative moment in the treatment of schizophrenia because, 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.
Rishi Kakar, MD, Chief scientific officer and Medical Director, Segal Trials and Investigator in the EMERGENT Program
Apart from this, Bristol Myers Squibb confirmed that the drug, unlike others, will not carry an FDA-boxed warning.
According to Adam Lenkowsky, chief commercialization officer for Bristol Myers Squibb (BMS), it has set a wholesale price of $1,850 a month, or around $22,500 a year.
What is so special about COBENFY?
Dr. Garrett Rossi, a psychiatrist and a content creator at Shrinks In Sneakers, posted a video on Instagram about the newly approved drug. In the video, he discussed how COBENFY became the first novel antipsychotic drug. He said that COBENFY works by modulating dopamine through M1 and M4 muscarinic agonism and offers treatment without the usual side effects like weight gain. Apart from this, he also mentioned that it also improves cognitive and negative symptoms, which wasn’t possible with the previous dopamine blockers. He also stressed the fact the clinical trial for this lasted for only 5 weeks and that schizophrenia requires longer-term treatment.
Today’s landmark approval of our first-in-class treatment for schizophrenia marks an important milestone for the community, where after more than 30 years, there is now an entirely new pharmacological approach for schizophrenia—one that has the potential to change the treatment paradigm. As we reenter the field of neuropsychiatry, we are dedicated to changing the conversation around serious mental illness, beginning with today’s approval in schizophrenia.
Chris Boerner, PhD, Board Chair and Chief Executive Officer at Bristol Myers Squibb
KEY HIGHLIGHTS:
The FDA announced the approval of Bristol Myers Squibb’s COBENFY for the treatment of schizophrenia.
It is a combination of xanomeline and trospium chloride.
The drug, unlike the previous antipsychotics, acts on M1 and M4 muscarinic receptors.
Emergent clinical trials were conducted to determine the safety, efficacy, and tolerability for 5 weeks.
At the end of the trials, the drug showed a reduction in symptoms, and improvement in illness, and reported fewer side effects.
It doesn’t have side effects like weight gain, which was the major issue with previous antipsychotics.
REFERENCES:
1. Schizophrenia - Symptoms and causes. (n.d.). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/schizophrenia/symptoms-causes/syc-20354443
2. Schizophrenia - Diagnosis and treatment - Mayo Clinic. (n.d.). https://www.mayoclinic.org/diseases-conditions/schizophrenia/diagnosis-treatment/drc-20354449
3. 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
4. https://www.fda.gov/news-events/press-announcements/fda-approves-drug-new-mechanism-action-treatment-schizophrenia
5. https://www.nytimes.com/2024/09/26/health/fda-schizophrenia-drug.html#
