CAPLYTA shows rapid improvement in bipolar mania in second pivotal Phase III study

Johnson & Johnson has reported positive results from Study 452, the second pivotal Phase III trial evaluating CAPLYTA in adults experiencing manic episodes associated with bipolar I disorder.

The randomised, double-blind study compared once-daily CAPLYTA 42 mg with placebo over three weeks in adults with manic episodes with or without mixed features.

The trial met its primary endpoint, with CAPLYTA producing a statistically significant improvement in Young Mania Rating Scale scores at Week 3.

Patients receiving CAPLYTA achieved a 3.7-point greater reduction in YMRS total score compared with placebo.

The effect size was -0.43, with a p value below 0.0001.

Significant improvement was observed as early as Day 3 and was maintained through Week 3.

Clinical response rates also favoured CAPLYTA.

At Week 3, 43.9% of patients receiving CAPLYTA achieved at least a 50% improvement from baseline in YMRS score compared with 23.7% of those receiving placebo.

The difference was statistically significant with a p value below 0.0001.

CAPLYTA also met the study’s key secondary endpoint assessing overall illness severity.

Patients receiving the treatment experienced a significantly greater improvement in Clinical Global Impression-Severity score compared with placebo at Week 3, with a least-squares mean difference of -0.41.

Improvement on this measure was also observed from Day 3.

Jane Tiller, FRCPsych, Vice President and Global Head of Development for Neuroscience at Johnson & Johnson, said the results add to evidence from the company’s first pivotal Phase III bipolar mania study and support the potential for CAPLYTA to address acute manic symptoms.

The safety and tolerability profile was consistent with previous studies of the treatment.

CAPLYTA was generally well tolerated, with low discontinuation rates.

The most common treatment-related adverse events occurring in at least 5% of patients and at least twice as frequently as with placebo were dizziness, dry mouth and somnolence or sedation.

The findings were presented as a late-breaking presentation at the 2026 Neuroscience Education Institute Fall Congress.

Study 452 follows previously reported positive results from Study 451.

Johnson & Johnson said the two Phase III studies will support a planned U.S. regulatory submission seeking approval of CAPLYTA for bipolar mania.

CAPLYTA, also known as lumateperone, is already approved in the U.S. for depressive episodes associated with bipolar I or II disorder, schizophrenia and as adjunctive treatment with antidepressants for major depressive disorder.

The medicine is not currently approved for the treatment of manic episodes associated with bipolar I disorder.

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Related Topics and Keywords

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