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August 10, 2022
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Karuna Therapeutics announces results from phase 3 trial of schizophrenia treatment

Fact checked byShenaz Bagha
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Karuna Therapeutics Inc. announced positive results from its phase 3 EMERGENT-2 trial evaluating the efficacy, safety and tolerability of its investigational therapy for adults with schizophrenia.

In a company release, Karuna said the trial met its primary endpoint, with KarXT (xanomeline-trospium), an oral, M1/M4-preferring muscarinic agonist, demonstrating a statistically significant and clinically meaningful 9.6-point reduction in the Positive and Negative Syndrome Scale (PANSS) total score compared to placebo (-21.2 KarXT vs. -11.6 placebo) at week 5.

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KarXT also demonstrated an early and sustained statistically significant reduction of symptoms as assessed by PANSS total score starting at week 2, and maintaining that reduction through all timepoints in the trial.

“We are thrilled that these topline results confirm what was seen in our Phase 2 EMERGENT-1 trial and underscore the potential for KarXT,” Steve Paul, MD, CEO, president and chairman of Karuna Therapeutics, said in the release.

According to the release, the phase 3 study was a placebo-controlled, 5-week, inpatient trial that included 252 U.S. adults between aged 18 to 65 years who were diagnosed with schizophrenia.

Patients were randomized on a 1:1 basis to receive either a flexible dose of KarXT (n=126) or placebo (n=126) twice per day for 5 weeks. On days 1 to 2, patients received a dose of 50/20 KarXT (50 mg xanomeline/20 mg trospium) or matching placebo. On day 3, patients escalated to a dose of 100 mg/20 mg, and starting on day 8, patients could increase to 125 mg/30 mg based on tolerability. During the trial, 81% of patients on KarXT compared with 90% on placebo titrated to the highest dose level (125/30).

The drug was generally well tolerated, with overall discontinuation rates similar between KarXT and placebo groups (25% vs. 21%). The overall treatment-emergent adverse events rate for KarXT and placebo was 75% and 58%, respectively.

Karuna says it will continue to gather long-term safety data to support eventual submission to the FDA of a new drug application for KarXT in mid-2023.