Phase III EMERGENT-2 trial of KarXT meets primary endpoint in adults with schizophrenia

The trial met its primary endpoint, with KarXT 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, p<0.0001) at week 5 (cohen’s d effect size of 0.61). karxt also demonstrated an early and sustained statistically significant reduction of symptoms, as assessed by panss total score, starting at week 2 and maintained such reduction through all timepoints in the trial.

KarXT also met key secondary endpoints in the Phase III EMERGENT-2 trial, demonstrating a statistically significant reduction in both positive symptoms (e.g., hallucinations or delusions) and negative symptoms (e.g., difficulty enjoying life or withdrawal from others) of schizophrenia as measured by the PANSS positive, PANSS negative and PANSS negative Marder factor subscales. Results at Week 5 include: a 2.9-point reduction in the PANSS positive subscale with KarXT compared to placebo (-6.8 KarXT vs. -3.9 placebo, p<0.0001). there is also a 1.8-point reduction in the panss negative subscale with karxt compared to placebo (-3.4 karxt vs. -1.6 placebo, p="0.0055)." finally there is a 2.2-point reduction in the panss negative marder factor subscale with karxt compared to placebo (-4.2 karxt vs. -2.0 placebo, p="0.0022)."

KarXT was generally well tolerated. Overall discontinuation rates were similar between KarXT and placebo groups (25% vs. 21%). The overall treatment-emergent adverse events (TEAEs) rate for KarXT and placebo was 75% and 58%, respectively. Discontinuation rates related to TEAEs were similar between KarXT (7%) and placebo (6%). Equal rates of serious TEAEs were observed between KarXT and placebo (2% in each group) and included suicidal ideation, worsening of schizophrenia symptoms, and appendicitis. None of the serious TEAEs were determined to be drug related. The data from the EMERGENT program will be used to support submission of an NDA with the U.S. FDA for KarXT as a treatment for schizophrenia, which is expected in mid-2023. Additional analysis of data from the Phase III EMERGENT-2 trial is ongoing, with plans to present these results at future medical meetings.