Bristol Myers Squibb’s schizophrenia drug Cobenfy brought in $27 million in net sales in the first three months of the year — beating Wall Street sales expectations and analyst predictions. Still, its strong debut doesn’t erase uncertainty around the drug, which just stumbled in the clinic, as BMS looks to answer high-stakes questions about its long-term market potential.
Cobenfy’s path to blockbuster sales hit a speed bump last week when the drug failed to improve symptoms more than a placebo in patients who took it alongside a second-generation antipsychotic. Despite the phase 3 setback, the company remained optimistic about the drug’s prospects, calling the data “encouraging” because patients showed improvement even if it wasn’t statistically significant.
But some experts, including Leerink Partners analysts, took the failed trial as a sign the drug may not live up to its early hype and downgraded their estimate for Cobenfy’s sales from $5.8 billion to $2.6 billion by 2030.
Even if Cobenfy doesn’t ultimately prove its worth as an add-on therapy, BMS is ramping up its clinical program for the treatment.
“This year, we will initiate seven phase 3 studies across three indications: Alzheimer's disease agitation, Alzheimer's disease cognition and bipolar I disorder,” a company spokesperson said via email. “And next year, we plan to begin phase 3 studies in autism spectrum disorder irritability.”
BMS expects phase 3 data from its Alzheimer’s psychosis trial in the second half of this year.
A promising option
BMS picked up Cobenfy (a combo of xanomeline and trospium chloride) as part of its $14 billion acquisition of Karuna Therapeutics. The drug gained FDA approval last year, becoming the first new type of schizophrenia medication on the market since the accidental discovery of the antipsychotic chlorpromazine in the 1950s.
While it fell short in the ARISE trial as an add-on therapy, another new batch of phase 3 data presented at the 2025 Schizophrenia International Research Society Annual Congress bolstered its case as a stand-alone schizophrenia therapy.
Results from its EMERGENT-4 and EMERGENT-5 trials released last year showed that patients saw significant improvements over baseline on the Positive and Negative Syndrome Scale of schizophrenia symptoms.
“Long-term treatment with Cobenfy was associated with continued, durable improvements in symptoms of schizophrenia across the PANSS total … and CGI-S score over 52 weeks,” Ken Kramer, vice president and head medical affairs, neuropsychiatry therapeutic area at BMS, said in an email. Patients on the drug had fewer hallucinations, delusions or disorganized behavior, and were also more physically active than before.
The company was encouraged to see the drug continued to improve symptoms and showed no new safety or tolerability concerns, Kramer said. In addition, there was no sign that efficacy waned in patients who took it for up to a year.
“These findings continue to reinforce our confidence in Cobenfy as an effective, long-term treatment option for adults with schizophrenia,” he said.
Much of the promise of the muscarinic agonist hinges on its improved side effect profile over traditional medications. All of the approved antipsychotics for schizophrenia work by targeting the dopamine D2 receptor or serotonin, and while they can improve symptoms, more than 70% of patients stop taking them due to side effects like weight gain.
Cobenfy’s also got side effect challenges.
More than 10% of patients who stopped taking the drug in the two phase 3 trials did so because of nausea, vomiting and constipation, according to Kramer.
“Nausea was among the most common [adverse event] associated with Cobenfy; however, nausea and vomiting often occurred during the first two weeks of treatment and generally decreased over time,” he said.
BMS will continue to study the drug in hopes of expanding its market, and plans to revisit data from the failed ARISE trial to see if there is a path forward for Cobenfy alongside other antipsychotic drugs.
“While the primary endpoint in this trial did not meet statistical significance, we need to complete our analysis and will plan to engage with the medical community and regulators to discuss these results and potential next steps,” Dr. Samit Hirawat, executive vice president, chief medical officer and head of development at Bristol Myers Squibb, said in a written release.
