Johnson & Johnson announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration for CAPLYTA (lumateperone) to prevent relapse in adults with schizophrenia, supported by Phase 3 data demonstrating a 63% reduction in relapse risk compared to placebo. The submission represents a significant expansion of the drug's approved indications and addresses a critical gap in long-term schizophrenia management.
Phase 3 Trial Results Show Significant Efficacy
The sNDA is based on positive results from Study 304, a multicenter, multinational, double-blind, placebo-controlled, randomized withdrawal trial. The study's primary endpoint showed that time to relapse during the 26-week double-blind treatment phase was significantly longer in patients receiving CAPLYTA compared to those receiving placebo (p=0.0002).
Treatment with CAPLYTA was associated with a 63% reduction in risk of relapse versus placebo, with a hazard ratio of 0.37 (95% CI: 0.22, 0.65). The key secondary endpoint demonstrated significantly delayed time to all-cause discontinuation, including relapse, compared with placebo during the double-blind phase (p=0.0007).
"CAPLYTA substantially lowers the chance of relapse for patients compared to placebo, which is often a major source of anxiety and suffering for them and their families," said Christoph U. Correll, M.D., Clinical Professor of Psychiatry at the Zucker School of Medicine at Hofstra/Northwell, New York.
Study Design and Patient Population
The approximately 47-week study included an 18-week open-label phase where patients with schizophrenia were treated with lumateperone 42 mg per day. Patients who met stabilization criteria during the open-label period progressed to the double-blind treatment phase, where they were randomized to continue on lumateperone 42 mg (N=114) or switched to placebo (N=114) for up to 26 weeks or until relapse occurred.
Addressing Critical Unmet Medical Need
Schizophrenia affects up to an estimated 2.8 million adults in the United States, yet remains insufficiently treated, with approximately 40% of people not receiving care. When left untreated, this complex mental health disorder can lead to episodes of psychosis, hallucinations, or other disruptive behaviors. Relapses are associated with significant functional decline, increased caregiver burden, and greater likelihood of hospitalization. On average, an adult with schizophrenia experiences nine relapses in less than six years.
"For people living with schizophrenia, relapses can be devastating as they disrupt lives, undo hard-earned treatment progress toward patients' goals, and increase the risk of hospitalization with each episode," Correll noted.
Safety Profile and Tolerability
The safety profile of CAPLYTA was consistent with the existing body of clinical data, and no new safety concerns were identified. The most commonly reported adverse event that was observed at a rate greater than or equal to 5% and twice the rate of placebo was headache.
In short-term clinical studies, CAPLYTA was similar to placebo in weight change, metabolic effects, and extrapyramidal symptoms, which are often cited as reasons for treatment discontinuation. The most commonly reported adverse events were somnolence/sedation, dizziness, nausea, and dry mouth.
Mechanism of Action and Current Approvals
While its exact mechanism of action is unknown, CAPLYTA is characterized by high serotonin 5-HT2A receptor occupancy and lower amounts of dopamine D2 receptor occupancy at therapeutic doses. The drug can be taken at any time of day with or without food and does not require titration, allowing adult patients to start treatment at the effective dose.
CAPLYTA is currently FDA approved for the treatment of schizophrenia, as well as depressive episodes associated with bipolar I or II disorder in adults, as monotherapy, and as adjunctive therapy with lithium or valproate. An sNDA for CAPLYTA as an adjunctive treatment for adults with major depressive disorder is currently under FDA review.
Strategic Significance for Johnson & Johnson
"Relapse prevention is a critical goal for the long-term care and management of this debilitating disorder," said Bill Martin, Ph.D., Global Therapeutic Area Head, Neuroscience, Johnson & Johnson Innovative Medicine. "These Phase 3 results provide compelling evidence of meaningful relapse prevention, which is critical in preserving long-term patient stability, breaking the cycle of hospitalization, and helping to control symptom progression."
With the addition of CAPLYTA to Johnson & Johnson's portfolio, the company now offers the broadest range of oral and long-acting injectable treatment options for adults with schizophrenia. If approved for relapse prevention, CAPLYTA has the potential to become a new standard of care for long-term schizophrenia management.
