Don Tracy, Associate Editor

A combination of data from the EMERGENT-4 trial and pooled data from the EMERGENT program showed the promise of KarXT (xanomeline-trospium) in providing symptom improvement for people with schizophrenia.

Bristol Myers Squibb announced results from its Phase III EMERGENT-4 trial analyzing the long-term efficacy, safety, and tolerability of KarXT (xanomeline-trospium) in adults with schizophrenia, which was showcased at the Annual Congress of the Schizophrenia International Research Society (SIRS). Additionally, the company revealed promising pooled data from EMERGENT-4 and EMERGENT-5 for the long-term safety, tolerability, and metabolic effects of KarXT in schizophrenia over 52 weeks.
EMERGENT-4 is a 52-week, open-label extension trial assessing long-term efficacy, safety, and tolerability of KarXT in adults who completed earlier phases of the trial for schizophrenia. Investigators found that over 75% of patients administered KarXT achieved a 30% improvement in symptoms.1
“We are pleased to see a continued and consistent meaningful reduction in symptoms of schizophrenia across 52-weeks in an outpatient setting, beyond what was seen in the short-term, in-patient five-week trials (EMERGENT-2 and EMERGENT-3),” said Roland Chen, MD, SVP, head, immunology, cardiovascular and neuroscience development, Bristol Myers Squibb, in a press release. “We look forward to continued conversations with the FDA and to sharing additional data from the EMERGENT program later this year.”
According to the pooled data from EMERGENT-4 and EMERGENT-5, 65% of patients experienced significant weight reduction, although no major changes were found in total cholesterol, triglycerides, and HbA1c levels. Further, KarXT was found to be well-tolerated with minor adverse effects (AEs). However, 53% of the study’s patients discontinued participation as a result of withdrawn consent and treatment-related AEs. Common AEs included nausea, vomiting, constipation, dry mouth, dyspepsia, dizziness, hypertension, and diarrhea. Further, 62% of patients reported experiencing at least one of these symptoms.2
“People living with schizophrenia and their care partners have long carried the burden of the condition, with a lack of treatment options that adequately treat the symptoms of schizophrenia without common debilitating side effects. To see that the long-term tolerability profile of KarXT remains consistent with earlier studies, where the cholinergic side effects of KarXT remained mainly mild or moderate in severity and were transient and resolving with continued treatment is very encouraging,” said Rishi Kakar, MD, chief scientific officer, medical director, Segal Trials, investigator in the EMERGENT program, in a press release. “These results are extremely promising and add to the growing body of data which suggest that, if approved, KarXT could provide a long-desired, differentiated treatment option for people living with schizophrenia.”
According to the World Health Organization (WHO), people with schizophrenia are more likely to die at an earlier age than the overall population, as a result of multiple physical illnesses. They also struggle with cognitive or thinking skills.3
“Schizophrenia affects approximately 24 million people or 1 in 300 people (0.32%) worldwide,” reports WHO. “This rate is 1 in 222 people (0.45%) among adults (2). It is not as common as many other mental disorders. Onset is most often during late adolescence and the twenties, and onset tends to happen earlier among men than among women.”