Johnson & Johnson has scored another major clinical trial success for CAPLYTA (lumateperone), with the drug meeting the primary and key secondary endpoints in its second pivotal Phase 3 study for treating manic episodes in adults with bipolar I disorder.
The positive results from Study 452 reinforce findings from the earlier Study 451, providing consistent evidence across two pivotal Phase 3 trials and paving the way for a planned US regulatory submission.
The study found that CAPLYTA significantly reduced manic symptoms and improved overall illness severity compared with placebo at Week 3. Notably, improvements were evident as early as Day 3, highlighting the drug's potential for rapid intervention during acute manic episodes.
“Manic episodes can disrupt a person’s safety, relationships, and daily life within days, underscoring the need for treatments that act rapidly,” said Jane Tiller, FRCPsych, Vice President, Global Head of Development, Neuroscience, Johnson & Johnson.
“Building on the established safety and efficacy profile of CAPLYTA in bipolar I and II depression, consistent, positive results across two pivotal Phase 3 studies in acute mania associated with bipolar I disorder support its potential to help stabilize symptoms for patients during some of the most difficult moments of their illness.”
Study 452 was a global, randomized, double-blind Phase 3 trial evaluating once-daily CAPLYTA 42 mg against placebo over three weeks in adults experiencing manic episodes, with or without mixed features, associated with bipolar I disorder (NCT06462612).
The drug delivered a statistically significant improvement on the Young Mania Rating Scale (YMRS), meeting the study's primary endpoint.
Patients receiving CAPLYTA experienced a 3.7-point greater reduction in YMRS total scores compared with those receiving placebo at Week 3. The improvement emerged as early as Day 3 and continued through the end of the study.
The response rates further strengthened the findings. Nearly twice as many patients treated with CAPLYTA achieved a clinical response, defined as at least a 50% improvement from baseline in YMRS scores, compared with placebo.
At Week 3, 43.9% of CAPLYTA-treated patients achieved this benchmark, against 23.7% in the placebo group.
CAPLYTA also cleared the key secondary endpoint, demonstrating significantly greater improvement in overall illness severity than placebo, as measured by the Clinical Global Impression–Severity (CGI-S) scale.
The least-squares mean difference was −0.41 at Week 3, with improvements again emerging as early as Day 3.
The results point to benefits extending beyond the reduction of manic symptoms, demonstrating improvement in the broader severity of the illness.
CAPLYTA was well-tolerated in Study 452, with low discontinuation rates and a safety profile consistent with findings from previous studies.
The most common treatment-related adverse events, reported in at least 5% of patients and at least twice as frequently as in the placebo group, were dizziness, dry mouth and somnolence/sedation.
With positive results now reported from both pivotal Phase 3 studies, Johnson & Johnson has strengthened the clinical evidence supporting CAPLYTA as a potential treatment for acute manic episodes associated with bipolar I disorder.
The company plans to use the findings from Studies 451 and 452 to support its forthcoming US regulatory submission.
