New data shows KarXT (xanomeline-trospium) has a favorable long-term metabolic profile in adults with schizophrenia, with patients experiencing metabolic stability or improvement during a 52-week treatment period.1 If approved by the U.S. Food and Drug Administration (FDA), KarXT would be the first new drug treatment for schizophrenia in decades.
Data from an emergency phase 3 program evaluating long-term safety, tolerability, and metabolic outcomes of KarXT in adults with schizophrenia were presented in a poster.2, 3 and oral session4,5 At the Annual Meeting of the Schizophrenia Research Society (SIRS), April 3-7, 2024 in Florence, Italy.
“Unlike current schizophrenia treatments, which are often associated with a variety of adverse events such as weight gain and hyperlipidemia, KarXT offers a new and unique mechanism of action that does not directly block dopamine receptors. KarXT offers a differentiated approach to the treatment of schizophrenia by exerting its effects on muscarinic receptors. This unique mechanism of action is responsible for the long-term favorable body weight and metabolic profile. We believe that there is,” said Dr. Rishi Kakkar. Psychiatry Times. Kakar is the chief scientific officer and medical director of Segal Trials and an investigator in the EMERGENT program.
The majority of patients (65%) experienced weight loss during the study period, with an average weight loss of 2.6 kg observed after 1 year. Data do not show significant prolactin-related changes or clinically meaningful changes in movement disorder scale scores over 52 weeks.
“Most patients suffering from schizophrenia in the community require long-term treatment for their symptoms. Therefore, it is important for clinicians to evaluate the potential effectiveness and safety of treatment options over time. The data presented at SIRS is an important milestone, highlighting the efficacy and safety of KarXT in clinical trials that lasted 52 weeks. In these long-term studies, KarXT “We found that there were no significant changes in cholesterol or hbA1c over time, and a favorable weight and metabolic profile with an average weight loss of 2.56 kg at 52 weeks,” Kakar said. Psychiatry Times. “Furthermore, the improvement in schizophrenia symptoms lasted for 52 weeks. This long-term data provides significant support for KarXT's potential as a unique first-in-class drug to treat schizophrenia.”
Phase 3 studies EMERGENT-4 and EMERGENT-5 are 52-week, open-label, outpatient studies evaluating the safety, tolerability, and efficacy of KarXT in adults with schizophrenia. As of August 18, 2023, the interim pooled data analysis included 718 patients who had received at least one dose of KarXT and 134 patients who had completed 1 year of treatment. Ta.
According to the integrated analysis, KarXT had a positive impact on body weight and long-term metabolic profile. Most patients experienced stabilization or improvement in key metabolic parameters during the 52-week treatment period, with 65% of patients experiencing overall weight loss during the study period and 18% of patients experiencing clinical Experienced potentially significant weight loss (>7%). 4% of patients experienced weight gain (≥7% change), whereas 4% of patients experienced weight gain (≥7% change). An average weight loss of 2.6 kg was observed in patients who completed his 52 weeks of treatment with KarXT, and an additional average weight loss of 4.1 kg in clinically obese patients (BMI > 30 kg/m2). There were no significant changes in total cholesterol, triglyceride, or HbA1c levels throughout the 1-year treatment.
“These long-term safety and metabolic results from the EMERGENT program are very encouraging and allow us to further understand the tolerability profile of KarXT in people living with schizophrenia.” said Roland Chen, MD, president and head of immunology and cardiovascular division. Neuroscience Development, Bristol-Myers Squibb Company. “It is encouraging that over one year of treatment, KarXT was not associated with troubling side effects, particularly weight gain, metabolic dysfunction, or extrapyramidal symptoms; It highlights the potential to offer meaningful and differentiated options to people living with schizophrenia. “1
Additionally, KarXT was generally well tolerated over the 52-week treatment period, and the side effect profile was consistent with previous trials. The study discontinuation rate was 53%, and the main reasons for discontinuation were withdrawal of consent (19%), treatment-related adverse events (15%), participants lost to follow-up (8%), and participants lost to the study plan. (7%).
Across all long-term EMERGENT trials, 62% of participants reported at least one treatment-related adverse event, with the most common treatment-related adverse events (≥5%) being nausea, vomiting, constipation, dry mouth, I had indigestion and was dizzy. , high blood pressure, diarrhea. Almost all symptoms were mild or moderate in severity and temporary in nature.
Additional interim long-term data presented at the conference showed that at 52 weeks in the EMERGENT-4 trial, KarXT was associated with significant improvements in schizophrenia symptoms across all efficacy measures. Improvement in schizophrenia symptoms continued during the open-label extension period, regardless of whether the participant was previously treated with her KarXT or placebo during the acute phase trial, EMERGENT-2 or EMERGENT-3 (Poster F264).
“When schizophrenia symptoms recur, patients' lives are significantly affected. For many patients, current treatments create an ongoing battle between controlling symptoms and managing side effects.” Although current treatments are partially effective, they often cause long-term side effect burdens such as weight gain, drowsiness, and metabolic effects, leading many patients to discontinue treatment. A unique first-in-class drug that combines a novel mechanism of action with a favorable long-term weight and metabolic profile, providing meaningful benefits to patients without the problematic long-term side effects of existing treatments. It has the potential to provide
BMS expects an FDA decision on potential approval of KarXT by September 26, 2024.
References
1. Bristol-Myers Squibb announced new interim long-term efficacy data from the EMERGENT-4 trial evaluating KarXT in schizophrenia at the 2024 Annual Meeting of the International Research Association for Schizophrenia. news release. April 6, 2024. Accessed April 7, 2024. https://news.bms.com/news/details/2024/Bristol-Myers-Squibb-Presents-New-Interim-Long-Term-Efficacy-Data-from-the -EMERGENT-4-Trial-Evaluating-KarXT- in-Schizophrenia-at-the-2024-Annual-Congress-of-the-Schizophrenia-International-Research-Society/default.aspx
2. Kaul I, Cohen EA, Miller AC, et al. Maintaining the effectiveness of her KarXT (xanomeline and trospium) in schizophrenia. Poster presentation location: Annual Conference of the International Research Association on Schizophrenia. April 3-7, 2024. Florence, Italy.
3. Marcus R, Kakar R, Miller AC, et al. Long-term safety of his KarXT (xanomeline and trospium) in schizophrenia. Poster presentation location: Annual Conference of the International Research Association on Schizophrenia. April 3-7, 2024. Florence, Italy.
4. Horan W, Sauder C, Harvey PD, et al. Effects of his KarXT on cognitive impairment in acute schizophrenia: Replication of pooled data from a phase 3 trial. Place of paper presentation: Annual Meeting of the International Research Association for Schizophrenia. April 3-7, 2024. Florence, Italy.
5. Claxton A, Konis G, Kaul I, et al. Long-term metabolic outcomes associated with KarXT (xanomeline and trospium): Interim results from the integrated long-term safety studies EMERGENT-4 and EMERGENT-5. Place of paper presentation: Annual Meeting of the International Research Association for Schizophrenia. April 3-7, 2024. Florence, Italy.