Caplyta Receives FDA Approval For Schizophrenia

The Food and Drug Administration (FDA) in December approved Caplyta (lumateperone), an oral antipsychotic medication to treat schizophrenia in adults.

According to the lumateperone label, the medication has been evaluated in 1,724 adult patients with schizophrenia exposed to one or more doses in placebo-controlled trials.

The details of one of those trials appeared in JAMA Psychiatry last month. According to the paper, 450 patients were randomized to one of three daily treatments: 42 mg of lumateperone, 28 mg of lumateperone, or placebo.

The primary endpoint was change in symptoms at 28 days as measured by the Positive and Negative Symptom Scale (PANSS). A secondary measure was the Clinical Global Impression of Severity (CGI-S) score, a seven-point clinician-rated scale of illness severity.

Patients who took 42 mg of lumateperone (but not those who took 28 mg of lumateperone) experienced a statistically significant decrease in symptoms over the four-week trial compared with those taking placebo, as measured by PANSS. Patients who took either dose of the medication also experienced significant improvements on the CGI-S. The drug appears to be safe. Weight gain and other metabolic changes, cardiac problems, or problems with movement or motor coordination were similar in study participants.

The study was supported by Intra-Cellular Therapies, which manufactures lumateperone.

The agent has attracted some optimism as a possible breakthrough in schizophrenia treatment because it acts on glutamate receptors in the brain as well as dopamine and serotonin receptors. Many of the so-called “me-too” second-generation antipsychotics (SGAs) manufactured in recent years have acted on serotonin and dopamine only; experts agree that what is needed to make a dramatic improvement in the lives of people with schizophrenia are medications that work on the brain in entirely novel ways.

In an editorial accompanying the study, Joshua Kantrowitz, M.D., of the Department of Psychiatry at Columbia University and the Nathan Kline Research Institute, expressed guarded optimism. “The relevance of an effective and potentially unique mechanism … could have an effect beyond lumateperone itself,” he wrote. “In recent years, multiple pharmaceutical companies have withdrawn from neuroscience research, and the success of lumateperone could spur additional research and development into novel mechanism research. After multiple high-profile failures, the field is risk averse. Thus, the stimulation of novel mechanism antipsychotic research could be as or more important than the role of lumateperone itself.”

William Carpenter, M.D., editor of Schizophrenia Bulletin and chair of the Psychotic Disorders workgroup for DSM-5, has been especially critical of manufacturer claims about me-too drugs.

“With so many me-too antipsychotic drugs available, is there reason to have higher expectations for lumateperone?” he asked. “It joins other drugs approved for schizophrenia in engaging dopaminergic pathways and appears to have a benign adverse effect profile. … While therapeutic advantages over current medications have not been reported, the mechanism simultaneously engaging dopaminergic, serotonergic, and glutamatergic networks is novel and merits further exploration.”

The labeling for lumateperone includes a boxed warning noting that older patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death. The medication is not approved for the treatment of patients with dementia-related psychosis. ■

“Efficacy and Safety of Lumateperone for Treatment of Schizophrenia: A Randomized Clinical Trial” is posted here. “The Potential Role of Lumateperone—Something Borrowed? Something New?” is posted here.