Kimberly E. Vanover
Results of a randomized clinical trial demonstrated a favorable safety profile and efficacy of lumateperone for patients with schizophrenia.
“Treatment with 42 mg of lumateperone met the primary efficacy objective in this study, significantly improving symptoms in adult patients with schizophrenia,” Kimberly E. Vanover, PhD, of Intra-Cellular Therapies Inc. in New York, told Healio Psychiatry. “Importantly, the agent's weight, metabolic and motor side effect profile was similar to placebo.”
Current antipsychotic therapy can effectively improve positive symptoms of schizophrenia, such as delusions and hallucinations, but it retains limited efficacy for negative symptoms, social functioning and cognitive impairment, Vanover and colleagues noted. Further, available treatments feature an array of adverse effects that “add to the already increased morbidity and mortality associated with schizophrenia.” Lumateperone offers a new avenue for treatment because it simultaneously modulates serotonin, dopamine and glutamate neurotransmission while also lacking interaction with off-target receptors potentially associated with the adverse effects of other antipsychotics, the researchers wrote.
The researchers conducted a randomized, double-blind, placebo-controlled, phase 3 clinical trial in 450 patients with schizophrenia aged 18 to 60 years who experienced an acute exacerbation of psychosis. As the pre-specified primary efficacy endpoint of lumateperone, they tested the mean change from baseline to day 28 in the Positive and Negative Syndrome Scale total score vs. placebo. The Clinical Global Impression-Severity of Illness (CGI-S) score was used as the key secondary efficacy measure.
According to a pre-specified modified intent-to-treat efficacy analysis, 42 mg of lumateperone met the primary and key secondary efficacy objectives. Thus, it demonstrated a statistically significant improvement vs. placebo from baseline to day 28 according to PANSS total score and the CGI-S. The least squares mean difference from baseline to day 28 for 28 mg of lumateperone was 2.6 (95% CI, 6.2 to 1.1) on the PANSS total score and 0.2 (95% CI, 0.5 to 0) on the CGI-S. Lumateperone demonstrated tolerability in both dosage amounts and its use did not result in clinically significant treatment-emergent motor adverse effects or changes in endocrine or cardiometabolic features compared with placebo.
“The efficacy and safety profile of lumateperone, as shown in this study and described in the prescribing information now approved by the FDA for adults with schizophrenia, offers health care providers an important new option for treating people living with schizophrenia,” Vanover said.
In a related editorial, Joshua T. Kantrowitz, MD, of the department of psychiatry at Columbia University, expressed a positive outlook for lumateperone’s continuing journey through the drug-approval pipeline.
“Moving from a positive phase 2 to a positive phase 3 study is often hazardous and unsuccessful,” Kantrowitz wrote. “Although we do not know what the ultimate comparative advantages of lumateperone will be, it is encouraging and potentially exciting to see a new drug with novel pharmacologic properties progressing through the gauntlet of drug development and [FDA] approval.” – by Joe Gramigna
Disclosures: Correll reports receiving personal fees from Intra-Cellular Therapies during the conduct of the study, as well as grants from Janssen and Takeda and personal fees from numerous pharmaceutical companies outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.