A promising drug for schizophrenia showed mixed results. What does that mean for patients?

Some people who took a new schizophrenia drug for a year improved with only a few side effects, but many dropped out of the study, the company announced Thursday.

The results underline the difficulties in treatment schizophrenia, a serious mental illness causing people to hear voices, feel paranoid, and withdraw from others. High dropout rates are characteristic of schizophrenia drug research.

Finding a drug that works can be a long ordeal, punctuated by crises and hospital admissions. Side effects of existing medications – weight gain, tremors, restlessness – cause some people to stop taking medications and relapse.

There is great hope among doctors for Cobenfy, which was approved in September, because it works differently in the brain than other drugs for schizophrenia. Instead of blocking dopamine receptors, Cobenfy’s main ingredient, xanomeline, works on another receptor that indirectly blocks the release of dopamine.

Cobenfy also contains trospium, which blocks some of the side effects. The most common are nausea, vomiting and indigestion. In contrast to the weight gain seen with other schizophrenia medications, people lost a few pounds while taking Cobenfy, made by Bristol Myers Squibb.

Dr. John Krystal of Yale University has led research into other drugs for schizophrenia, but was not involved in the new studies. He noted that only 10% to 20% of participants in the new studies dropped out because of side effects.

“That’s pretty good,” he said, noting that fewer or milder side effects could help people stay in treatment longer. That could mean fewer problems associated with untreated mental health conditions: substance use, homelessness and unemployment.

So why did some patients continue treatment while others stopped? Krystal said it will be important to learn more about that when doctors start prescribing the drug.

The Food and Drug Administration approved Cobenfy based on two encouraging five-week company-sponsored studies and other safety data. The latest results announced Thursday at the Psych Congress meeting in Boston come from two longer studies, which provide a fuller picture.

In one study, focused on critically ill patients, 78% dropped out, leaving just 35 people for the final analysis. In the other, aimed at more stable people, 51% left the study, leaving 283 who took the drug for a year.

“It’s no higher or lower than what we typically see” in studies of schizophrenia, said Dr. Greg Mattingly of the Washington University School of Medicine in St. Louis. Mattingly is a consultant for Bristol Myers Squibb and an investigator on one of the studies.

In the more seriously ill group, 69% of people had meaningful improvement in their symptoms by the end of the year. In the other group, 30% saw a meaningful benefit.

The results of interviews with a sample of study participants, conducted by an independent research team and shared by Bristol Myers Squibb, indicated that it was likely that treatment would continue. After six months, 36 said they would continue using Cobenfy after the trial if given the option; 10 said they wouldn’t. Some participants said the drug muffled their voices, while others said it didn’t work for them.

The estimated annual cost for Cobenfy is $22,500, compared to $540 for a generic antipsychotic. Krystal and others worry that insurers will require people to try cheaper drugs first before covering Cobenfy. The out-of-pocket costs for most patients will be much lower, depending on insurance and other factors.

A cheaper generic drug called clozapine is widely considered one of the best treatments for schizophrenia, Krystal said. It is underutilized in the US compared to some other countries due to a cumbersome blood testing program.

The FDA has started blood tests to watch for the risk of severe neutropenia, a rare side effect that can be fatal. But doctors and families have told the FDA that patients have relapsed when their clozapine was withheld or delayed because of testing requirements.

Sally Littlefield, 29, of Alameda, California, said what works for her is a monthly injection of a long-acting antipsychotic. Littlefield, who has schizophrenia and bipolar disorder, wants to learn more about the experiences of people who have used Cobenfy and not just players with a financial interest.

Mindy Greiling of Roseville, Minnesota, wants to see data on how Cobenfy compares to clozapine, which works for her 47-year-old son Jim. Weight gain has been a problem for him, but since taking diabetes medication, he has returned to his normal weight, Greiling said.

Cobenfy “receives a lot of criticism, like any new drug,” Greiling said. “It’s a non-starter for me unless it turns out to be better than clozapine.”

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