In a move that could reshape long-term schizophrenia care, Johnson & Johnson has announced that it’s submitted a supplemental New Drug Application (sNDA) for Caplyta (lumateperone). The pharmaceutical giant wants the U.S. Food and Drug Administration (FDA) to let them update the antipsychotic’s label, based on promising trial results.
Executives based their decision on encouraging topline results from the drug’s developer (and J&J subsidiary), Intra-Cellular Therapies. Study 304 – a huge Phase 3 randomized withdrawal trial – affirmed the drug’s ability to work as an effective schizophrenia maintenance treatment. In short, patients treated with lumateperone enjoyed a much longer time to relapse compared to those on a placebo, with a 63% reduction in relapse risk.
“For people living with schizophrenia, relapses can be devastating as they disrupt lives, undo hard-earned progress, and increase hospitalization risk with each episode,” Christoph Correll, MD, clinical professor of psychiatry at the Zucker School of Medicine at Hofstra/Northwell, elaborated. “Caplyta substantially lowers the chance of relapse compared to placebo, which is often a major source of anxiety for patients and families alike.”
Topline Results
Study 304, which ran for nearly a year, included an 18-week open-label phase where researchers treated adult schizophrenia patients with a 42 mg dose of Caplyta every day. Researchers then randomized the stabilized participants into a 26-week double-blind phase, where they either kept taking Caplyta or switched to placebo.
The study hit the primary endpoint — time to first symptom relapse — with statistical significance (p=0.0002). Only 16.4% of patients on Caplyta relapsed, compared to 38.6% in the placebo group. This translated to a hazard ratio of 0.37, revealing a 63% reduced risk of relapse. Caplyta also showed dramatic benefits on the critical secondary endpoint: time to all-cause treatment discontinuation (p=0.0007).
“The control of symptoms and prevention of relapse is critical to improving long-term outcomes,” Intra-Cellular Therapies Executive Vice President and Chief Medical Officer Suresh Durgam, MD, added.
A Robust Safety Profile
Both J&J and Intra-Cellular Therapies stressed that Caplyta’s safety profile remained consistent with earlier studies. Researchers identified no new safety concerns, and the adverse events that cropped up were “generally manageable.” Headaches emerged as the most frequently reported side effect, occurring at a rate higher than the placebo.
Caplyta also showed a favorable metabolic and neurological safety profile in short-term trials. That’s a noteworthy competitive advantage in a drug class typically associated with weight gain, diabetes risk, and extrapyramidal symptoms (such as tremors or rigidity). The most frequent side effects included somnolence, dizziness, nausea, and dry mouth.
Critically, Caplyta doesn’t demand dose titration and patients only have to take it once a day, with or without food. It’s an attribute that makes treatment easier, boosting adherence rates.
“Relapse prevention is a critical goal for long-term care,” J&J Global Therapeutic Area Head, Neuroscience, Bill Martin, PhD, said. “These Phase 3 results provide compelling evidence that Caplyta can help preserve patient stability, break the cycle of hospitalization, and potentially slow disease progression.”
Broader Implications
Caplyta’s already earned FDA approval for depressive episodes associated with bipolar I or II disorder, either as monotherapy or as an adjunct to lithium or valproate.
J&J is also looking for FDA approval for its use as an adjunctive treatment for major depressive disorder (MDD).
Caplyta’s mechanism of action involves high affinity for serotonin 5-HT2A receptors and moderate dopamine D2 receptor activity, allowing it to effectively balance neurotransmitter activity responsible for psychosis and mood disorders. And even though researchers are still trying to pin down the precise mechanics involved, Caplyta’s dual receptor profile sets it apart from legacy antipsychotics.
The scientists at Intra-Cellular Therapies are still exploring lumateperone’s potential in treating other conditions, including MDD. But the FDA has yet to sign off on any other applications.
Safety Considerations and Warnings
As with so many other antipsychotics, Caplyta carries a boxed warning regarding increased mortality in elderly patients with dementia-related psychosis. The literature also warns of potential risks for suicidal thoughts and behaviors in young adults and pediatric patients.
Additional safety considerations include risks for neuroleptic malignant syndrome (a rare but serious reaction), tardive dyskinesia, metabolic changes, blood pressure irregularities, and falls due to sedation or dizziness. Researchers insist that patients with a history of seizures or those at risk for aspiration should receive close supervision. Drug interactions, particularly with CYP3A4 inducers and inhibitors, could obviously require dosage adjustments.
Despite these cautions, Caplyta’s overall safety and tolerability profile continues to make it an appealing option for long-term use in schizophrenia and bipolar depression.
Industry Implications
The latest data could give J&J and Intra-Cellular Therapies an edge (at least for now) in an increasingly competitive mental health therapeutics market, particularly as treatment goals shift focus to long-term functional recovery.
With its favorable safety profile, ease of use, and strong relapse prevention data, Caplyta could soon earn an expanded FDA label – cementing its place as a mainstay therapy for schizophrenia and potentially extending its reach into other major psychiatric conditions.
“Patients deserve therapies that not only address symptoms in the short term but also support long-term stability and quality of life,” Martin added. “These results underscore Caplyta’s potential to do just that.”
Further Reading
New Insights Into Xanomeline/Trospium
Antipsychotic Adherence Halves Crash Risk for Drivers with Schizophrenia
Children of Parents with Schizophrenia Face More Mental Health Issues
