What the heck is going on when you feel the need to go on and off, and what you don’t want to do: A study of Cobenfy, a muscarinic receptor antagonist

She says to just keep trying. “It’s really hard to go on and off medications, but when you find the right one, it makes a huge difference — night and day.”

“Every time I have an episode, I lose bits of myself and bits of functionality … and that’s not fair to my husband, and I hate it,” she says. If I could get something that would help me get more involved, that would be terrific.

Tiffany would like to try the drug down the road. Cobenfy has been shown to decrease the negative symptoms of scholids, like apathy and lack of motivation, unlike previous drugs which only tackled the positive symptoms.

The FDA based its approval on 5-week double-blind, placebo-controlled studies. Some patients received Cobenfy and some got placebo, but nobody knew which until the study ended. Some experts have pointed out that questions still remain about the drug’s long-term safety and efficacy, despite the short study length.

Patients and their parents are excited about the possibilities of a new treatment option, he says. Ballon is working on an ongoing study of how Cobenfy fits in with existing drugs and whether they can be used together.

Other drug makers are following strategies to improve the profile of KarXT. Some are developing formulations with more convenient dosing schedules. KarXT does not have both the M4 and the M1 muscarinic receptors, but others are trying to design compounds that only use one or both for cognitive and antipsychotic effects.

So Miller and his team decided to add a second medicine — one already used for overactive bladder — to shut down the gastrointestinal receptors. The trick: That medication can’t cross into the brain from the blood.

The first schizophrenia drug with an antipsychotic mechanism of action has marketed well, but few patients have insurance for Cobenfy, a company owned by Bristol Myers Squibb

She is talking about Miller and his company, Karuna, which was acquired by pharmaceutical giant BristolMyers Squibb for over fourteen billion dollars this year.

The drug will be priced at $1,850 a month and will be in line with other schizophrenia treatments. It’s unclear how easy it will be for patients to get insurance coverage for Cobenfy.

If it’s like many of the other new medications, people will be required to try at least two generic drugs before they will pay for it, says Jacob Ballon, an associate professor of psychiatry.

Dopamine is the neurotransmitter usually associated with reward and learning, but it actually has a lot of functions. It also plays a role in controlling movement, for example — that’s why that one drug made Tiffany pace.

Dr. Ann Shinn says that the dopamine hypothesis suggested that schizophrenia was associated with excessive dopamine activity.

The first schizophrenia medication in decades with a new mechanism of action won US regulatory approval today. The approval offers the hope that an antipsychotic would work and be more effective than the current therapies.

She tried different pills until she found the one that worked for her. Some of the effects were brutal. Common antipsychotic drugs can cause weight gain and increase the risk for diabetes.

An Alternative Therapies for Schizophrenics: A Case Study on KarXT, a New Antipsychotic Drug Named Cobenfy

Everyone was happy when I opened presents. And I’m just sitting there like, there’s nothing going on. Like, I’m staring at a blank wall,” she says. I lied to them and said that I was better.

When she was first put on an antipsychotic drug, she says it made her feel like a zombie. She didn’t recognize herself while viewing a video of her birthday party.

Tiffany, a librarian in Oklahoma, is paying attention to the difference. We were asked to only use her first name because of the stigma associated with schizophrenia.

The drug named KarXT was referred to as Cobenfy during the development of the pill. The main advantage of it is that it has less side effects than the current medicines.

In some trials, the two-in-one pill was more effective in treating schizophrenia than placebo, without the weight gain, sedation, or movement issues associated with existing anti-psychotics. The side effects of KarXT were mostly in the form of gut disturbances, which would clear after a week or two of use.

It is apparent that drug developers and clinicians hope that treatment for schizophrenia will become more tailored to individual needs in the future, so people who don’t benefit from current therapies can at least have an alternative.

“This provides an option that is completely outside the toolbox that we have right now,” says Ann Shinn, a psychiatrist at McLean Hospital in Belmont, Massachusetts, who has no commercial ties to KarXT.

Exploiting the potential for therapy of schizophrenia using muscarinic signalling: CEO Steven Paul welcomes the innovation in injecting xanomeline with trospium

It was shown by the trials that the drug offered both cognitive and mental benefits. But xanomeline also caused nausea, vomiting and stomach pain — because muscarinic receptors are active in the gut as well as the brain — leading Lilly to ultimately shelve the drug.

In 2009, Miller formed a company called Karuna. Karuna combined xanomeline with a drug called trospium. This well-understood molecule blocks muscarinic receptors and does not cross the blood–brain barrier, meaning that it selectively prevents side effects in the gut without interfering with xanomeline’s action in the brain.

The drug has some flaws. It requires twice-daily administration, and studies suggest that having more frequent dosages is related to higher rates of non-adherence and treatment cessation in people with schizophrenia. “That’s a big limitation,” says Nate Sutera, a psychiatric pharmacist at the University of Nebraska Medical Center in Omaha — particularly because many antipsychotics are now available as long-acting injectables, requiring only a few doses annually.

KarXT also comes with an anticipated price tag of roughly US$20,000 per year7, raising concerns among health economists about its cost-effectiveness compared with alternatives. Despite this, most industry analysts predict strong demand, with peak annual sales projected in the billions. This potential was a key factor in BristolMyers Squibb acquiring Karuna for over $13 billion this year.

Former Karuna chief executive Steven Paul, a psychiatrist now at the Washington University School of Medicine in St. Louis, Missouri, welcomes the wave of innovation in targeting muscarinic signalling that KarXT helped to unleash — and he looks forward to discovering the best ways to harness this therapeutic strategy.

He says that they have new biology and pharmacology to explore. “It will be fun and scientifically relevant — and, hopefully, clinically beneficial to patients — to find out.”

The medication is the first in decades to have a different mode of action than current drugs, achieving better symptom relief with fewer side effects.