Can Cobenfy Help People With Schizophrenia?

Summary: Yes, according to the research that led to its approval, the new medication Cobenfy can help people with schizophrenia in ways that previous generations of medication for schizophrenia and schizoaffective disorder cannot.

Key Points:

• The first line treatment for schizophrenia is medication with first- and second-generation antipsychotics
• Antipsychotic medications are effective in reducing some but not all the symptoms of schizophrenia.
• Antipsychotics have significant side effects that often lead to voluntary discontinuation, which impairs long-term outcomes for people in treatment for schizophrenia.
• This new medication can help people with schizophrenia by addressing more symptoms and limiting uncomfortable side effects.

About Schizophrenia: Prevalence and Symptoms

Schizophrenia is a complex mental health disorder that can cause serious impairment in all areas of life and is associated with significant functional disability. The 2023 publication “Mental and Substance Use Disorders Prevalence Study: Findings Report” shows the following prevalence of schizophrenia among adults in the U.S.:

• Lifetime diagnosis, adults 18-65: Approximately 3.7 million, or 1.8%
• Past-year diagnosis, adults 18-65: 2.5 million, or 1.2%

Experts divide the symptoms of schizophrenia into three primary types: positive, negative, and cognitive:

1. Positive symptoms such as hallucinations, delusions, disordered thoughts, and atypical, repetitive movements can both confuse and frighten you and the people close to you.
2. Negative symptoms like loss of motivation, withdrawal from social life, difficulty expressing emotions, and difficulties with basic functioning can create challenges in relationships, academics, and work/vocational pursuits.
3. Cognitive symptoms impair thinking, reasoning, memory, problem-solving, decision-making, and learning not only have a negative impact on basic functioning in relationships, school, and work, but also things like engaging in coherent, productive conversations with others and being consistent with keeping appointments and managing daily responsibilities.

As we indicate above, these symptoms can cause serious disruption in daily life and significant impairment in daily life. Current medications for schizophrenia are effective at reducing many of the positive symptoms of schizophrenia, but are not as effective in reducing the negative and cognitive symptoms of schizophrenia. In addition, the significant side effects of first- and second-generation antipsychotics lead to resistance to treatment in about a third of people with schizophrenia.

That’s why this new medication is promising. Not only does it reduce all three types of symptoms associated with schizophrenia, it also has a more tolerable set of side effects, which may mean more people adhere to treatment, which leads to positive outcomes overall.

Let’s take a closer look at Cobenfy, and why the F.D.A. approved it as a new treatment to help people with schizophrenia.

What is Cobenfy?

In September 2024, the U.S. Food and Drug Administration (FDA) approved a new schizophrenia medication called Cobenfy. This is a new antipsychotic medication that works differently than previous generations of antipsychotics. Rather than targeting dopamine receptors in the human brain, the active components target cholinergic receptors. This is a significant step for schizophrenia treatment for at least two reasons:

1. It’s the first new medication approved for schizophrenia in 30 years.
2. It contains an additional medication designed to mitigate problematic side effects.

Here’s how Dr. Tiffany Farchione, director of the Division of Psychiatry for Drug Evaluation and Research at the FDA, views the approval of Cobenfy:

“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. This drug takes the first new approach to schizophrenia treatment in decades. This approval offers a new alternative to the antipsychotic medications people with schizophrenia have previously been prescribed.

Cobenfy is formulated by combining two existing medications:

• Xanomeline, a new schizophrenia medication, previously used alone, without combining with other medications, also studied for treatment of Alzheimer’s disease.
• Trospium chloride, a medication previously used to treat urinary incontinence/overactive bladder (OAB).

The studies that led to the approval of Cobenfy showed the following:

• Significant reductions in positive symptoms measured by the Positive and Negative Syndrome Scale (PANSS)
• Significant reductions in negative symptoms measured by PANSS
• Fewer problematic side effects than first- and second-generation antipsychotic medications, including fewer instances of
  • Weight gain
  • Movement disorders

In addition, a series of secondary studies showed:

• Improvement in cognitive scores on the Cambridge Neuropsychological Test Automated Battery (CANTAB) for patients with pre-existing cognitive deficits
• Improvements appeared in questions assessing verbal memory, recall, and recognition

Dr. William Horan, a researcher working on these secondary studies, offered this insight:

“[This is]…the first time a monotherapy for the treatment of schizophrenia has shown a replicable cognitive benefit.”

We’ll discuss these results – and the approval of Cobenfy by the F.D.A – below.

How Cobenfy May Help Our Patients

People with schizophrenia often find themselves in a multi-level bind:

1. They don’t want to experience the symptoms of schizophrenia.
2. The only medications that help their symptoms make them feel physically terrible.
3. The only medications that help their symptoms can give them movement disorders, and don’t have much impact on negative symptoms and cognitive symptoms.
4. They discontinue treatment because of the side effects and dissatisfaction with symptom improvement.
5. Discontinuation results in a return of symptoms and a return of functional impairment.

Not only can discontinuation lead to a return of symptoms and impairment, but it can also create conflict with loved ones and family members and have a negative impact on the treatment alliance patients establish with their psychiatrist or psychotherapist.

According to the F.D.A. approved research, Cobenfy has the potential to dramatically change treatment for schizophrenia. A new medication that can improve positive and negative symptoms in most patients, cognitive symptoms in some patients, without the extreme and problematic side effects associated with previous antipsychotics, may be the difference that keeps patients in treatment, on their medication, and gives them a greater chance of long-term emotional and psychological stability.

The authors of the study Cobenfy (Xanomeline-Trospium): A Breakthrough FDA-Approved Therapy Redefining Schizophrenia Treatment describe the approval of this medication as follows:

“By addressing the full spectrum of symptoms and reducing the burden of side effect…this ‘miracle drug’ not only sets a new benchmark in schizophrenia management but also serves as an inspiration for future therapeutic breakthroughs in the field.”

Is Cobenfy really a miracle drug? Time will tell. What we know now is that there’s new tool in our toolbox that may be helpful for our patients with schizophrenia.