This week, however, the U.S. Food and Drug Administration (FDA) approved a new drug — Caplyta (lumateperone), which will give people living with schizophrenia a new approach to treatment. It is expected to be available in early 2020. “Schizophrenia is a challenging disease to manage — it is marked by cycles of relapse and incomplete recovery,” says Andrew Satlin, MD, chief medical officer at Intra-Cellular Therapies, the biopharmaceutical company that manufactures the drug. “Caplyta offers healthcare providers a new, safe, and effective option for treating people living with schizophrenia.”
Drug Passes Latest Hurdles After Initial Difficulties
The FDA greenlighted the medication in a daily oral dose of 42 milligrams after it showed significant benefit over placebo in two trials. The drug demonstrated clinical efficacy on the Positive and Negative Syndrome Scale (PANSS), a tool used to measure symptom severity in schizophrenia. The “positive” symptoms (although not positive in the traditional sense of the word) are psychotic behaviors that include hallucinations, delusions, thought disorders, and movement disorder, while the negative symptoms are connected to emotions and behaviors and include reduced feelings of pleasure, limited speaking, and “flat affect.” Antipsychotics typically relieve the positive symptoms, according to the Treatment Advocacy Center. Previously, the drug had mixed results in studies. In a test of 696 patients in 2016, Caplyta failed to meet its primary end point. In July 2019, the FDA cancelled an advisory committee meeting regarding the medication in order to review more information.
Approval Comes With Warning About Risks
The FDA issued a black box warning, the agency’s most serious type of advisory, which notes an increased mortality in elderly patients with dementia-related psychosis. The warning states that Caplyta is not approved for the treatment of patients with dementia-related psychosis.
A Novel Therapy With Fewer Side Effects
Caplyta works through a unique targeting of serotonin, dopamine, and glutamate neurotransmitters in the brain. “Although the exact way the drug works is unknown, it is thought to improve dysfunction through several effects on nerve cell chemicals and their receptors,” says Dr. Satlin. The dominant therapeutic approach for schizophrenia has been to modulate dopamine neurotransmission. “We need more medications like this one that work differently and don’t just mediate the dopamine receptors,” says Linda Stalters, a master of science in nursing and the chief executive officer of Schizophrenia and Related Disorders Alliance of America (SARDAA). “Patients are screaming to have more and better medications.” While the latest studies, according to a press release, showed that Caplyta caused some tiredness (24 percent in the drug group versus 10 percent in the placebo group) and dry mouth (6 percent versus 2 percent), the medication had promising results when it came to metabolic changes. Weight gain, fasting glucose, triglycerides, and total cholesterol were about the same in both the Caplyta and placebo groups. “Often one of the side effects with schizophrenia medication is metabolic disorder where patients start gaining a lot of weight, and with that comes high cholesterol, diabetes, high blood pressure, and cardiovascular disease,” says Stalters. Caplyta also did not cause akathisia, a feeling of jitteriness among patients, which is extraordinarily uncomfortable and makes people “jump out of their skin,” the company says. Satlin adds that the drug had a favorable profile when it comes to restlessness and other movement issues.
Promising Signs But Proceed With Caution
Scott Krakower, DO, an assistant unit chief in the psychiatry department at Zucker Hillside Hospital in Glen Oaks, New York, sees promise in this new agent to improve quality of life and function for patients. “The current drugs aren’t always effective,” he says. “Some patients have no response, partial response, or weight gain or restlessness — so it’s always good to have more options, provided they are safe.” Research has shown that people with schizophrenia often have trouble sticking to their treatment plan. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study found that 74 percent of patients had discontinued medication within 18 months due to insufficient efficacy, intolerable side effects, or for other reasons. “If there are more agents out there that are better tolerated and there isn’t weight gain, there may be more compliance,” says Dr. Krakower. “And that is something we are aiming for in patients with schizophrenia.” Despite the positive indications so far, Krakower also warns that the true effectiveness of the drug can only be gauged once it’s being used by a broader population. “Whenever any new medication comes out on the market, we have to be very cautious — there is a possibility the agent won’t work out,” he says. “Patients should still be considering all the options out there for schizophrenia and they should speak to their practitioner to decide on what is the best medication.”
