Sixty-five percent of patients lost weight. That is one of the findings from a year-long look at Bristol Myers Squibb’s new schizophrenia drug, which the U.S. Food and Drug Administration approved on Sept. 26 as Cobenfy, also known as KarXT, a combination of xanomeline and trospium.
It is the first non-dopaminergic treatment option for the illness. “Today’s approval is a significant milestone for the schizophrenia community,” company CEO Chris Boerner, PhD, said in a press release. “For the first time in more than 30 years, we have a new pharmacological approach with the potential to change the treatment landscape.”
What the studies looked at
The data come from EMERGENT-4 and EMERGENT-5, the latest phase 3, multicenter, outpatient, open-label studies of the drug. Company officials first reported the results in April at the Annual Congress of the Schizophrenia International Research Society in Florence, Italy. Adults with schizophrenia started on 50 mg/20 mg twice daily, and doses were later raised to a maximum of 125 mg/30 mg twice daily.
The main goal was long-term safety and tolerability. Researchers measured efficacy as the change from baseline on the Positive and Negative Syndrome Scale (PANSS).
EMERGENT-4 enrolled people who had finished one of two earlier double-blind, placebo-controlled trials, EMERGENT-2 or EMERGENT-3, which tested the drug in patients having an episode of acute psychosis. EMERGENT-5 was a stand-alone trial that included patients with a new diagnosis. The interim EMERGENT-4 efficacy data covered 110 patients, 48 of whom had been treated with KarXT before. The pooled safety and metabolic analysis covered 718 patients who got at least one dose, 134 of whom completed a year.
Weight and metabolic results
Over 52 weeks, 65 percent of participants lost weight, averaging 2.6 kg. Patients with obesity, defined as a BMI above 30 kg/m, lost more, an average of 4.07 kg. A potentially clinically significant weight decrease, meaning a drop of more than 7 percent from baseline, showed up in 17.6 percent of patients. A gain of the same size occurred in 4.1 percent.
Total cholesterol, triglycerides and A1C levels showed no clinically meaningful change after a year.
Side effects and dropouts
Across the EMERGENT trials, 62 percent of patients reported at least one treatment-related adverse event. Side effects seen in more than 5 percent of cases were mild and transient: nausea, vomiting, constipation, dry mouth, dyspepsia, dizziness, hypertension and diarrhea. Prolactin and movement-disorder scale scores showed no clinical or significant impact.
Fifty-three percent of patients left the trial. Of those, 15 percent left because of treatment-emergent adverse events.
“It is promising to see that, over one year of treatment, KarXT was not associated with burdensome side effects, specifically weight gain and metabolic dysfunction, as well as extrapyramidal symptoms,” said Roland Chen, MD, a senior vice president at Bristol Myers Squibb.
At 52 weeks, symptoms improved across all efficacy measures in the EMERGENT-4 extension. Rishi Kakar, MD, an investigator in the program and Chief Scientific Officer at Segal Trials, said the cholinergic side effects stayed mostly mild or moderate, were transient, and resolved with continued treatment. He called that “very encouraging.”
Anyone weighing a switch from their current medication should talk to their doctor first.
