5 Things to Know About Cobenfy — Plus Updates on Other Schizophrenia Medications in Development

Your upbringing, environment, and mindset can all impact how you perceive the world. Certain health conditions also play a role. And for people living with schizophrenia, their thoughts and behaviors may not line up with what other people around them are seeing or hearing.

The best way to treat schizophrenia is different for everyone. Many people benefit from different types of therapy, such as personal or group therapy. Antipsychotic medications are also recommended, but their side effects and ability to manage symptoms aren't always ideal.

With these drawbacks, health experts are looking into new treatments for schizophrenia. And the fruits of this labor are starting to pay off. One new medication, called Cobenfy (formerly known as KarXT), was FDA approved for adults living with schizophrenia in late September 2024. Many other medications are following in its footsteps in clinical trials, too.

Here, we'll dive into the top five things to know about Cobenfy for schizophrenia. We'll also highlight other medications that may be available down the line.

1. Cobenfy is a new schizophrenia medication

Cobenfy is an oral schizophrenia medication for adults. It's available with a prescription, and it contains two active ingredients - xanomeline and trospium chloride. You or a loved one can take it as a maintenance medication to manage schizophrenia symptoms over time.

Cobenfy is unique because it works differently from other medications that are currently approved for schizophrenia. According to its manufacturer, it's the first new type of schizophrenia medication to be approved in several decades.

Some psychiatrists may opt to prescribe Cobenfy by itself, while others may prescribe it in combination with antipsychotics.

2. Cobenfy doesn't work by affecting dopamine receptors

Cobenfy is a combination of xanomeline and trospium chloride. Xanomeline is a muscarinic agonist, and trospium is a muscarinic antagonist (also called an anticholinergic). They do opposite things in your body, but for good reason.

Xanomeline stimulates specific muscarinic receptors (chemical binding sites) in your brain. These receptors are located in parts of your brain involved in thinking and behavior. Stimulating these receptors is thought to help lessen symptoms of schizophrenia. But xanomeline can affect your whole body - not just your brain. This can cause bothersome side effects, such as sweating, diarrhea, and too much salivation.

This is where trospium chloride comes in. It blocks muscarinic receptors throughout your body, but it doesn't cross into your brain. This helps minimize xanomeline's side effects while still allowing it to work.

By comparison, antipsychotic medications work differently. They impact hormones like dopamine and serotonin.

3. Cobenfy's recommended dosages are relatively simple

Cobenfy is an oral capsule taken 2 times per day. You should take your doses about 1 hour before meals or 2 hours after.

The amount of medicine you'll take per capsule varies - especially when you're first starting the medication.

You should start off by taking one 50 mg/20 mg capsule twice daily. After a couple of days, your prescriber will likely bump up your dose to 100 mg/20 mg twice daily. This may be the dose you stick with, especially if it's working well to address your symptoms. But if your body doesn't respond to it, your prescriber may increase the dose again to 125 mg/30 mg.

For reference, Cobenfy capsules come in three different dosages. Each one contains a different amount of xanomeline and trospium chloride, respectively: 50 mg/20 mg, 100 mg/20 mg, and 125 mg/30 mg.

Good to know: Recommended Cobenfy dosages can vary for different people. For instance, older adults may stick to lower doses to minimize side effects. Your prescriber may also adjust your dose if they notice a drug interaction on your medication list. However, if you have liver problems or biliary disease, you'll likely avoid the medication altogether.

4. Cobenfy's clinical trial results were positive overall

Cobenfy was studied in a few clinical trials. One phase 3 trial was called EMERGENT-2. It was a 5-week study that included about 250 adults with schizophrenia. About half of them took Cobenfy, and the other half took a placebo (a pill with no medication in it). Cobenfy was significantly better than placebo at reducing the severity of schizophrenia-related symptoms. But a few steps went into this finding.

The study used a scoring system called the Positive and Negative Syndrome Scale (PANSS). PANSS is a go-to test in schizophrenia studies when determining how effective a treatment is. Mild schizophrenia symptoms can get a score as low as 30, and severe symptoms can get a score as high as 210.

Over the course of the study, people taking Cobenfy saw their PANSS score drop by more than 21 points on average. People taking placebo saw their scores go down by about 12 points.

Another phase 3 trial, known as EMERGENT-3, was conducted in a similar manner and had comparable results.

5. There are still some Cobenfy side effects to consider

Cobenfy is relatively well-tolerated overall. But it's still been linked to some side effects. The most common Cobenfy (KarXT) side effects include:

• Nausea and vomiting

• Upset stomach

• Constipation

• Diarrhea

• Bloating

• Stomach pain

• Acid reflux

• Dizziness

• Headache

• High blood pressure

More serious risks and side effects have also been reported, but they're less common:

• Urinary retention (difficulty releasing urine)

• Heart rate changes

• Increased liver enzymes

• Less movement in your gastrointestinal tract

• Angle-closure glaucoma

• Angioedema (face, neck, or mouth swelling)

Contact your prescriber if you experience any bothersome side effects while taking Cobenfy. But if something feels severe, make sure to listen to your body; call 911 or seek emergency medical attention.

What other non-antipsychotic medications are being studied for schizophrenia?

Other non-antipsychotic medications are being studied for schizophrenia too. Some are in the later stages of development, and others are just getting started.

In general, completing a phase 3 clinical trial is the last big step before a medication is submitted to the FDA for approval. A few medications are in these advanced stages.

Ulotaront

Ulotaront (SEP-363856) is an oral tablet being studied for schizophrenia in people ages 13 and older. It works in a unique way - it targets a receptor called trace amine-associated receptor 1 (TAAR1). Some health experts think targeting this receptor may help with general schizophrenia symptoms.

So far, two phase 3 studies for ulotaront reported negative results. But the journey isn't over; another ulotaront phase 3 study is expected to finish in early 2025.

Iclepertin

Iclepertin (BI 425809) is an oral tablet being studied for schizophrenia in adults. Researchers are looking to see if it improves thinking and memory symptoms that are worsened by schizophrenia. It works by blocking a protein called glycine transporter-1 (GlyT1) in the brain.

Iclepertin's three phase 3 trials (CONNEX-1, CONNEX-2, and CONNEX-3) are set to wrap up by the end of 2024. The study findings should be published by early 2025. The FDA gave it a Breakthrough Therapy Designation in May 2021.

Valbenazine

Valbenazine (Ingrezza) is currently approved to treat tardive dyskinesia and Huntington's disease. But it's also being studied as an additional treatment for schizophrenia in people ages 13 and older. It's an oral capsule that blocks a protein called vesicular monoamine transporter 2 (VMAT2).

In a phase 3 trial, researchers are looking to see if valbenazine can help improve schizophrenia symptoms in people who didn't respond well to antipsychotics. The study should finish up by March 2025.

Early-stage clinical trials

Many more medications are going through earlier-stage studies. This isn't an exhaustive list, but these medications hypothetically could be approved for schizophrenia down the line.

What medications are currently recommended for schizophrenia?

Antipsychotics are currently the recommended schizophrenia medications. They can manage schizophrenia-related symptoms and promote positive changes in thoughts and behavior.

One antipsychotic isn't widely considered to be better than the rest. Rather, the best one tends to come down to response, personal preferences, and side effects. They're also grouped into two categories.

Most of these medications are oral pills that are taken every day. But many antipsychotics are also available as long-acting injections. This allows you to go longer between doses. These are some common examples:

• Risperidone (Risperdal Consta), injected every 2 weeks

• Olanzapine (Zyprexa Relprevv), injected every 2-4 weeks

• Aripiprazole (Abilify Maintena), injected every month

• Paliperidone (Invega Sustenna, Erzofri), injected every month

• Aripiprazole lauroxil (Aristada), injected every 1-2 months

• Risperidone (Uzedy), injected every 1-2 months

• Paliperidone (Invega Trinza), injected every 3 months

• Paliperidone (Invega Hafyera), injected every 6 months