As Johnson & Johnson’s $14.6 billion bet on Intra-Cellular Therapies continues to pay off with blockbuster sales of Caplyta, the atypical antipsychotic has passed a phase 3 test that puts it one step closer to a wider psychiatric label.
Caplyta (lumateperone), first approved back in 2019 under Intra-Cellular’s stewardship for schizophrenia, helped deliver rapid improvement in manic symptoms and improved overall illness severity, among other benefits versus placebo, over three weeks in a late-stage trial in adults with manic episodes associated with bipolar I disorder, J&J said in a release Monday.
The results, which pointed to improvements in bipolar mania on Caplyta starting as early as day 3 of treatment, were presented with a clutch of other J&J readouts at the recent 2026 Psych Congress annual meeting in New Orleans. The study, coded 451, is part of a pair looking at Caplyta in adults with bipolar I-associated manic episodes.
Multiple decades-old drugs exist to treat such episodes, including the mood stabilizer lithium, plus antiseizure medications like carbamazepine and valproate that fulfill a similar function, as well as other atypical antipsychotics.
Nevertheless, J&J believes that tolerability issues and the variable responses patients experience on existing treatments for manic episodes make the case for an option like Caplyta.
"Mania is among the most dangerous and worrisome phases of bipolar disorder, and treating it effectively takes more than partial or temporary relief of symptoms,” said Michael Thase, M.D., a professor of psychiatry at the University of Pennsylvania, in J&J’s release.
Bringing those episodes under control “as quickly as possible” is also paramount, he said, pointing back to the three-day onset of benefit seen in J&J's Study 451.
The trial specifically assessed Caplyta at 42 mg in adults with bipolar I-associated manic episodes with or without mixed features, which refers to symptoms of mania mixed with those of depression.
By demonstrating a 4.8-point greater reduction on a measure of manic symptoms at three weeks versus placebo, Caplyta helped the study meet its primary endpoint, with J&J flagging “significant improvement” as early as day 3 and sustained through the full 21-day trial period.
Patients on the J&J drug also saw significantly greater improvement in overall illness severity compared with placebo at week three on another clinical metric, which formed one of the trial’s key secondary endpoints.
J&J also pointed out that more than twice as many patients on Caplyta achieved a clinical response, using the same Young Mania Rating Scale underpinning the primary endpoint, at 45.8%, versus 20.9% of patients in the control cohort.
Caplyta was well tolerated in the study and did not raise any new safety flags beyond its known profile, J&J said.
"These Phase 3 results build on the established efficacy of Caplyta in bipolar depression and represent an important step in evaluating its potential to address both depressive and acute manic episodes associated with bipolar I disorder,” said J&J’s global head of neuroscience development, Jane Tiller, in a statement.
J&J’s second phase 3 study of Caplyta in adults with bipolar I-associated manic episodes has already wrapped up, and data analysis is ongoing, the drugmaker added.
Apart from its inaugural schizophrenia nod, Caplyta was approved by the FDA in 2021 to treat bipolar depression and more recently as an add-on treatment for major depressive disorder (MDD) last November.
J&J has forecasted multiple billions of dollars in potential peak sales of Caplyta, which opened a sizeable new patient front with its MDD nod last year.
J&J got its hands on the drug by way of its $14.6 billion buyout of Intra-Cellular early last year, inspired in large part by the medicine’s MDD aspirations.