Johnson & Johnson is gearing up to expand the commercial reach of Caplyta after scoring a second phase 3 victory in bipolar mania.
The second phase 3 trial evaluating Caplyta (lumateperone) for treating manic episodes in patients with bipolar I disorder met its primary endpoint, showing a statistically significant improvement in manic symptoms compared with placebo at week 3, J&J said Tuesday.
Key secondary endpoints, such as overall illness severity at week 3, were also met. And the drug’s tolerability profile was consistent with prior studies, J&J said.
The readout comes from Study 452, the second pivotal trial win for Caplyta in bipolar mania following the successful Study 451. Touting “consistent evidence” from two phase 3 studies, J&J said the combined data will support its planned submission for an FDA approval.
Caplyta is already approved by the FDA to treat schizophrenia, depressive episodes associated with bipolar I or II and as an adjunctive therapy for major depressive disorder. Bipolar disorder affects an estimated 36 million people globally, and manic episodes can escalate quickly to often require hospitalization, according to J&J.
“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,” Jane Tiller, J&J’s neuroscience global head of development, said in a Nov. 10 statement.
Digging into the specific data. Caplyta achieved a 3.7-point greater reduction from baseline in the Young Mania Rating Scale (YMRS) total score compared with placebo at week 3. Previously, in Study 451, Caplyta delivered a 4.8-point advantage on YMRS versus placebo.
In the current study, at week 3, 43.9% of patients receiving Caplyta had at least a 50% improvement from baseline on the YMRS score, compared with 23.7% in the control group. In Study 451, the rates were 45.8% versus 20.9%, respectively.
J&J also touted Caplyta’s rapid onset of benefit, with symptom improvements emerging as early as the third day. On the trial’s secondary endpoint measuring overall illness severity, as measured by the Clinical Global Impression-Severity (CGI-S) scale, Caplyta delivered a least-squares mean difference of 0.41 versus placebo, similar to the 0.5 it drove in the other phase 3.
The looming label expansion for Caplyta underscores J&J’s deepening position in neuroscience, a therapeutic area where the company has shown a willingness to make some bold bets.
J&J brought Caplyta under its wings through its $14.6 billion acquisition of Intra-Cellular Therapeutics in 2025. About seven years ago, the Big Pharma company introduced ketamine-based Spravato to the market and turned it into a blockbuster antidepressant.
In the third quarter, J&J reported U.S. Caplyta sales of $398 million, while Spravato generated $624 million worldwide.
J&J is now throwing its weight behind the burgeoning psychedelics sector. On Monday, J&J’s venture capital arm, Johnson & Johnson Innovation, led a $100 million series C financing round for Delix Therapeutics. The Massachusetts-based biotech is engineering non-hallucinogenic analogs, with its lead asset, a once-daily pill dubbed zalsupindole, moving into a phase 2 trial for major depressive disorder.