BackSchizophrenia treatment may finally be worth talking about
Next year, doctors might finally have something new to offer people who suffer from schizophrenia: a much-needed drug that can better improve their symptoms without side effects that too often cause them to stop taking their medications
PremiumNext year, doctors might finally have something new to offer people who suffer from schizophrenia: a much-needed drug that can better improve their symptoms without side effects that too often cause them to stop taking their medications.
The latest round of late-stage data on a drug in development by Karuna Therapeutics, released on Monday, reinforces its potential to offer desperately needed progress for a brain disorder that affects about 1% of people in the US.
Karuna’s news is a bit of a revival story. One component of the treatment, called xanomeline, has been around since the early 1990s, when scientists at Eli Lilly started exploring its use to treat the cognitive and behavioural symptoms of Alzheimer’s disease and, later, schizophrenia.
Small studies suggested the drug could have a marked effect on those symptoms, but it was dropped from development because people could not tolerate its side effects. The problem was that the drug didn’t act only on receptors that carry messages between nerve cells in the brain, but interacted with ones throughout the whole body, causing people who took it to get nauseated and vomit.
Typically, the next step would have been to go back to design a new molecule that retains the good parts of the drug while avoiding its nasty gastrointestinal side effects. But xanomeline came along when the currently available anti-psychotics, which mainly work by slowing down dopamine signalling in the brain, were coming on to the market. With other drugs quickly achieving blockbuster sales status and scientists convinced it would be folly to try to engineer out the bad bits of xanomeline, companies abandoned that drug and others like it.
That is, until many years later when Karuna struck upon a different tack. Rather than try to build a new drug from scratch, what if it combined xanomeline with a drug that could dampen the side effects? It turns out such a drug already existed. A drug for overactive bladder syndrome called trospium blocks muscarinic receptors outside the brain, thereby mostly limiting xanomeline’s effects to the brain.
This week’s data provides more evidence that Karuna’s approach is working. Schizophrenia encompasses a constellation of symptoms, and the study achieved its primary goal of demonstrating that the Karuna drug could decrease ones like paranoia, delusions and hallucinations. Just as important, it not only helped people without the tough side effects of xanomeline on its own, but also avoids the weight gain or drowsiness associated with all the currently available classes of schizophrenia drugs—side effects that often cause people to stop taking those treatments.
This new batch of data wasn’t a total slam dunk. The company’s stock traded down on Monday, seemingly because investors were unhappy with a continuing sign that some patients on the drug experienced elevated blood pressure. But it’s worth noting that the side effect didn’t cause people to drop out of the trial and that the magnitude of the effect diminished during the trial; Karuna is exploring the issue in a separate safety study.
In this trial, the drug also failed to have a statistically significant effect on what are known as negative symptoms of schizophrenia. Those are qualities that are diminished in people with schizophrenia compared with those without the disease, such as emotional and verbal engagement with the world, motivation and the ability to experience pleasure. Those negative components affect some 60% of people with schizophrenia.
These caveats don’t mean the drug won’t win approval from the US Food and Drug Administration, which is expected in the second half of 2024.
But it does leave an opening for other treatments in development that take a different approach to tinkering with the activity of muscarinic receptors. Efforts worth watching include a drug in mid-stage clinical trials by Cerevel Therapeutics and earlier-stage drugs discovered by researchers at Vanderbilt University’s Warren Center for Neuroscience Drug Discovery.
As the market reacts to this new batch of data, I keep coming back to something a psychiatrist once told me about drug development for schizophrenia: Perfect is the enemy of the good. Maybe Karuna’s drug doesn’t end up being the right choice for everyone, but helping even a fraction of the population could make a huge difference in the lives of hundreds of thousands of people. And ultimately, it moves the needle closer to drugs that can holistically and safely treat all the symptoms of schizophrenia. That’s the kind of advance this field needs and people with schizophrenia deserve.
Lisa Jarvis is a Bloomberg Opinion columnist covering biotech, health care and the pharmaceutical industry.
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