Potential ‘Game-Changer’
Xanomeline-trospium is a potential “game-changer” for patients with schizophrenia, Ann Shinn, MD, MPH, director of clinical research, Schizophrenia and Bipolar Disorder Research Program, McLean Hospital, and assistant professor of psychiatry, Harvard Medical School, told this news organization.
There was a “clear separation between the people who were randomized to KarXT vs placebo. It’s not just a statistically significant but also a clinically significant difference in the reduction in symptoms of psychosis,” said Dr. Shinn, who wasn’t involved in the study.
“What’s really exciting” is that the drug did not cause weight gain or extrapyramidal symptoms compared with placebo. “Both from an efficacy and side-effect perspective, I think more patients with schizophrenia are going to be willing to take medication,” Dr. Shinn noted.
Also commenting on this research for this news organization, René Kahn, MD, PhD, professor and chair of psychiatry at the Icahn School of Medicine at Mount Sinai in New York, noted that current antipsychotic medications for schizophrenia work “directly on the dopamine system — either as dopamine antagonists or partial agonist.”
Xanomeline-trospium provides a “new mechanism of action, a new system that’s being targeted in the treatment of schizophrenia, and the effect size was rather large, so the drug didn’t just squeak by,” Dr. Kahn said.
Nonetheless, “we’ll have to wait and see whether it’s as effective or more effective than drugs currently on the market. The proof of the pudding will come when it’s marketed and used on thousands and thousands of patients,” Dr. Kahn added.
The coauthors of an accompanying commentary say the EMERGENT-2 findings “strongly support the possibility that agonism of muscarinic receptors provides the first viable antipsychotic alternative to blocking the dopamine D2 receptor for more than 70 years, and as such encourage further research.”
However, as a regulatory trial, EMERGENT-2 does not provide comparative data on the benefits and harms of KarXT with existing alternatives.
This represents a “missed opportunity to provide patients and clinicians with the information that is clinically needed — what is the treatment of choice for a patient?” writes Andrea Cipriani, MD, PhD, with the Department of Psychiatry, University of Oxford, United Kingdom, and co-authors.
The study was funded by Karuna Therapeutics. Several authors disclosed relationships with the company. Dr. Kahn disclosed various relationships with Boehringer Ingelheim International GmbH. Dr. Cipriani received research, educational, and consultancy fees from the Italian Network for Paediatric Trials, the CARIPLO Foundation, Lundbeck, and Angelini Pharma and was chief investigator of one trial about seltorexant in adolescent depression, sponsored by Janssen. Dr. Shinn had no relevant disclosures.
A version of this article appeared on Medscape.com.