Journal Publication Brings Good News for Novel Schizophrenia Treatment


The chief medical officer of Karuna shares his thoughts exclusively with Psychiatric Times.



The New England Journal of Medicine has published the encouraging results of Karuna Therapeutics’ EMERGENT-1 phase 2 clinical trial for their novel treatment, KarXT. A proprietary oral modulator of muscarinic cholinergic receptors, KarXT offers a new approach to treating patients with schizophrenia.

In an exclusive quote to Psychiatric TimesTM, Steve Brannan, MD, chief medical officer of Karuna Therapeutics and lead author of the manuscript, had this to say: “The findings published in the New England Journal of Medicine from the EMERGENT-1 Phase 2 trial further support the potential impact we believe KarXT can have on addressing schizophrenia with a new mechanism of action to effectively treat the condition, while lessening the concerning side effects seen in the current standard of care. Overall, we are encouraged by the data generated to-date and look forward to continuing to progress the EMERGENT clinical program through Phase 3 studies.”

The manuscript, Muscarinic Cholinergic Receptor Agonist and Peripheral Antagonist for Schizophrenia, shares promising data.1 The EMERGENT-1 phase 2 trial lasted 5 weeks and enrolled 182 adults with an acute exacerbation of schizophrenia. Treatment with a twice-daily, flexible-dose of KarXT demonstrated a statistically significant and clinically meaningful 11.6-point reduction in the Positive and Negative Syndrome Scale (PANSS) total score compared to placebo at week 5.

Additionally, 4 of the 5 prespecified secondary outcome measures showed statistically significant reductions for the KarXT group compared to placebo at Week 5. These secondary outcome measures included PANSS positive symptom subscore, PANSS negative symptom subscore, PANSS Marder negative symptom subscore, and Clinical Global Impression – Severity frequency counts.

“Many people living with schizophrenia have persistent symptoms, experience poor quality of life and impaired ability to function, despite treatment with current antipsychotic drugs,” said Jeffrey Lieberman, MD, professor and chairman of the department of psychiatry at Columbia University, and coauthor of the manuscript. “The clinical trial results with KarXT highlight its potential to be a differentiated treatment option with a completely new mechanism of action for people living with schizophrenia, offering relief from acute psychotic symptoms without the debilitating side effects associated with the current standard of care.”2

KarXT was generally well-tolerated, with the most common adverse events being constipation, nausea, dry mouth, dyspepsia and vomiting, though all were mild-to-moderate in severity and were not associated with treatment discontinuation. Rates of nausea, vomiting, and dry mouth decreased over the course of the trial, while rates of constipation remained constant. Both the placebo and KarXT treatment groups showed incidences of somnolence, weight gain, and extrapyramidal symptoms, which are common problematic side effects of current antipsychotic therapies.

“These findings support the potential for KarXT to treat symptoms of psychosis in schizophrenia without producing the common problematic side effects of current therapies, such as weight gain and extrapyramidal symptoms. Given these encouraging results, we have advanced KarXT into Phase 3 clinical development in our efforts to provide a meaningful, new, non-dopaminergic treatment option for this serious neuropsychiatric disorder affecting more than 21 million people worldwide,” Brannan said further.2


1. Brannan SK, Sawchak S, Miller AC, et al. Muscarinic cholinergic receptor agonist and peripheral antagonist for schizophrenia. N Engl J Med. February 25, 2021.

2. Karuna Therapeutics. Karuna Therapeutics announces New England Journal of Medicine publication of data from EMERGENT-1 Phase 2 trial evaluating KarXT in schizophrenia. News release. February 24, 2021.

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