Johnson & Johnson announced that the US FDA has approved a supplemental New Drug Application (sNDA) for Caplyta (lumateperone) for the prevention of relapse in schizophrenia. The approval adds a long-term maintenance indication to a drug already cleared for acute schizophrenia, major depressive disorder, and bipolar depression, and represents the first FDA approval of lumateperone specifically for relapse prevention in schizophrenia.
The sNDA was supported by long-term Phase III data from Study 304, a multicenter, randomized withdrawal, double-blind, placebo-controlled trial. Caplyta is administered as a 42 mg oral once-daily capsule, and no titration is required. The drug’s mechanism involves high serotonin 5-HT2A receptor occupancy and moderate dopamine D2 receptor occupancy at therapeutic doses, though the company states the exact mechanism of action remains unknown.
The pivotal Study 304 enrolled 224 adults with schizophrenia in an 18-week open-label phase during which patients received lumateperone 42 mg daily. Those who met stabilization criteria were then randomized to continue on lumateperone (N=110) or switch to placebo (N=114) for up to 26 weeks. The primary endpoint was time to first symptom relapse during the double-blind phase. Patients receiving Caplyta had a 63% lower risk of relapse compared with placebo, with a hazard ratio of 0.37 and a statistically significant extension of time to relapse (p=0.0002). 84% of patients in the lumateperone arm remained relapse-free over six months. The drug also significantly delayed time to all-cause treatment discontinuation. The safety profile was consistent with prior studies, with headache reported as the most common treatment-related adverse event, occurring in at least 5% of patients and at twice the rate of placebo. A 12-month open-label extension showed a mean weight change of -2.05 kg, with stability in metabolic parameters.