- Johnson & Johnson: FDA approved sNDA for CAPLYTA (lumateperone) to prevent schizophrenia relapse, with Phase 3 Study 304 showing 63% lower relapse risk (HR 0.37) and 84% relapse‑free at 26 weeks.
- Study 304 design: 18‑week open‑label lumateperone 42 mg lead‑in, then randomized withdrawal to continue lumateperone (N=110) or switch to placebo (N=114) for up to 26 weeks.
- Safety and tolerability remained consistent with no new signals; most common treatment‑related AE was headache (≥5% and ≥2× placebo) and 12‑month open‑label data showed mean weight change −2.05 kg.
FDA approval and indication
The FDA approved a supplemental New Drug Application for CAPLYTA (lumateperone) to prevent relapse in adults with schizophrenia; CAPLYTA is already approved for schizophrenia, adjunctive major depressive disorder, and bipolar depression (monotherapy and adjunctive with lithium or valproate).
Phase 3 relapse‑prevention trial (Study 304)
Study 304 was a multicenter, multinational randomized‑withdrawal trial with an 18‑week open‑label lead‑in of lumateperone 42 mg daily; stabilized patients were randomized to continue lumateperone (N=110) or switch to placebo (N=114) for up to 26 weeks. CAPLYTA significantly extended time to relapse versus placebo (p=0.0002), with a hazard ratio of 0.37 (63% lower relapse risk) and 84% of patients relapse‑free at 26 weeks; it also delayed time to all‑cause treatment discontinuation.
Safety and longer‑term data
The double‑blind safety profile was consistent with prior data and showed no new signals; the most common treatment‑related adverse event was headache (≥5% and ≥2× placebo). No clinically relevant increases in prolactin or cardiometabolic parameters were observed at the end of the double‑blind period. A 12‑month open‑label extension reported a mean weight change of −2.05 kg and sustained improvements or stability in metabolic measures.
Pharmacology
Lumateperone’s mechanism is not fully defined; at therapeutic doses it shows high serotonin 5‑HT2A receptor occupancy and moderate dopamine D2 receptor occupancy.
