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The Food and Drug Administration has approved Cobenfy, a twice-daily drug that is a new type of treatment for schizophrenia in adults.
Steve Belkowitz/Bristol Myers Squibb
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Steve Belkowitz/Bristol Myers Squibb
For the first time in decades, the Food and Drug Administration has approved a new type of drug for schizophrenia.
The twice-daily pill to be marketed by Bristol Myers Squibb will be called Cobenfy, although it was referred to as KarXT during development. Its main advantage is that it appears to have fewer side effects than current medications.
That difference has caught the attention of patients like Tiffany, a librarian in Oklahoma. She asked that we use only her first name because of the stigma associated with schizophrenia.
When she was first given an antipsychotic, she says she felt like a zombie. When she saw a video of her birthday party that year, she didn’t recognize herself.
“I was opening presents – everyone was happy. And I just sit there, nothing’s happening. Like I’m staring at a blank wall,” she says. “And so I lied and told everyone I was better.”
So she stopped taking the drug and continued to struggle with it for years, until she experienced another psychotic episode.
She then played what she calls the “drug game,” trying different pills until one worked for her. But some side effects were brutal. Common antipsychotic medications can cause weight gain and increase the risk of diabetes.
One of these gave Tiffany a movement disorder.
“So I was pacing around my office for eight hours a day, and it’s exactly 3 1/2 steps, turn, 3 1/2 steps, turn,” she says. “It was a nightmare.”
Decades of dopamine-targeted drugs
Since the first antipsychotic drug was introduced in the 1950s, subsequent medications for treating psychosis work on the same chemical that helps the brain communicate with the rest of the body: dopamine.
“The dopamine hypothesis proposed that schizophrenia is associated with excessive dopamine neurotransmission – so too much dopamine activity,” says Dr. Ann Shinna psychiatrist who directs clinical research on schizophrenia and bipolar disorder at McLean Hospital near Boston.
Dopamine is the neurotransmitter commonly associated with reward and learning, but it actually has many functions. For example, it also plays a role in controlling movements. That’s why that one drug made Tiffany faster.
The new drug targets different brain receptors
Cobenfy is the first new drug against psychosis that does not act on dopamine.
“I got really interested in schizophrenia and through that work I got really interested in the idea of targeting muscarinic receptors because here was a serendipitous clinical finding that suggested potential efficacy, which is very difficult to obtain in psychiatry,” says the lead inventor of the medicine. Andreas Molenaar.
He talks about a 1997 study of Alzheimer’s patients about a drug that was shelved even though it reduced psychosis.
The muscarinic receptors got their name because they respond to muscarinic, a chemical in some mushrooms. The problem with developing a drug to activate them in the brain is that they can activate receptors in the gastrointestinal tract. Patients could not tolerate it.
So Miller and his team decided to add a second drug — one already used for overactive bladder — to disable the gastrointestinal receptors. The trick: the medicine cannot pass from the blood into the brain.
That means it shuts down the body’s muscarinic receptors, but doesn’t stop the first drug from doing its work in the brain.
“Karuna has actually done the brilliant thing of putting everything together in a combination drug,” says Shinn.
She’s talking about Miller’s company, Karuna Therapeutics, which was acquired by pharmaceutical heavyweight Bristol Myers Squibb for $14 billion dollars earlier this year.
How much will it cost?
Bristol Myers Squibb says the drug will be available starting in October for $1,850 per month, which is in line with other treatments for schizophrenia. It’s unclear how easy it will be for patients to get insurance coverage for Cobenfy.
“If it’s like many other new drugs, insurance will generally require that people try at least two generic drugs first… before paying for them,” said Dr. Jacob Ballon, an associate professor of psychiatry at Stanford University. .
Still, he says, he has many patients – and their parents – who are excited about a possible new treatment option. Ballon is working on an ongoing study into how Cobenfy fits into existing medications and whether they can be used together.
While the new drug isn’t for everyone, it could help patients who have had problems with existing treatments.
The FDA based its approval on double-blind, placebo-controlled, five-week studies. That means some patients were given Cobenfy and others were given a placebo, but neither the patients nor the doctors knew which was which until the study was over. The short duration of the study has prompted some experts to point out that questions remain about the drug’s long-term safety and efficacy.
Common side effects of Cobenfy include nausea, constipation and fast heart rate.
As for Tiffany, she is interested in trying the drug later. Unlike previous medications that only addressed the so-called positive symptoms of schizophrenia, such as hallucinations and delusions, Cobenfy has been shown to reduce the ‘negative’ symptoms, such as apathy and lack of motivation.
“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. “So if I could have something that would help me take a little more initiative, that would be great.”
She also has advice for people with schizophrenia who are still looking for the right treatment.
“Just keep trying,” she says. “It’s very difficult to take and stop medications, but if you find the right one, it makes a huge difference – night and day.”
