J&J’s Caplyta hits goals in bipolar mania trial

Unbranded psychiatric medication capsules near trial documents after positive bipolar mania Phase 3 results

Key Points

01Caplyta met primary and key secondary endpoints in Phase 3 Study 452 for bipolar mania
02Treatment achieved a 3.7‑point greater Week 3 YMRS reduction versus placebo with significance
03A higher rate of clinical response (at least 50% improvement from baseline on the YMRS total score) occurred with CAPLYTA versus placebo at Week 3.
04Two positive Phase 3 studies will support a planned U.S. FDA submission for bipolar mania

Second pivotal Phase 3 study reaches main goals

Johnson & Johnson (JNJ) reported that CAPLYTA (lumateperone) achieved its primary and key secondary endpoints in a second pivotal Phase 3 trial, Study 452, in adults experiencing manic episodes associated with bipolar I disorder. The global, randomized, double-blind study compared once-daily CAPLYTA 42 mg with placebo over three weeks and forms part of the program intended to support a planned U.S. FDA submission for bipolar mania.

At Week 3, CAPLYTA produced a statistically significant 3.7‑point greater reduction in Young Mania Rating Scale (YMRS) total score versus placebo, with an effect size of −0.43 and P<.0001. Johnson & Johnson said improvement in manic symptoms appeared as early as Day 3 and was sustained through the three‑week treatment period, indicating rapid and maintained benefit in the study population.

Clinical response and overall illness severity

Johnson & Johnson said a higher rate of clinical response occurred, defined as at least a 50% improvement from baseline on the YMRS total score.

Benefit extended beyond mania scores to overall illness severity, measured by the Clinical Global Impression–Severity (CGI‑S) scale. The key secondary endpoint was met, with a least squares mean difference of −0.41 versus placebo at Week 3 and P=.0003, and improvement on this measure was also seen as early as Day 3.

Safety, tolerability and regulatory plans

Johnson & Johnson said CAPLYTA was well‑tolerated, with low rates of discontinuation and a safety and tolerability profile consistent with prior experience for the medicine.

The positive outcome of Study 452, together with results from a prior pivotal Phase 3 trial, will underpin a planned U.S. FDA submission to expand CAPLYTA’s use to the treatment of manic episodes associated with bipolar I disorder. CAPLYTA is not currently approved for bipolar mania, but is approved in adults for depressive episodes associated with bipolar I or II disorder, schizophrenia and as adjunctive therapy with antidepressants for major depressive disorder.

Key Takeaways

01Caplyta delivered rapid and sustained reductions in manic symptoms, with statistically significant YMRS improvements emerging by Day 3 and maintained through Week 3.
02The drug improved both specific mania scores and broader illness severity measures, suggesting a consistent clinical effect across multiple endpoints.
03Safety findings in the trial aligned with Caplyta’s existing profile, supporting Johnson & Johnson (JNJ)’s plan to seek a U.S. FDA label expansion into bipolar mania.

References