“A New and Differentiated Approach for Schizophrenia”: Positive Results for Phase 3 Trial

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Positive topline results for the phase 3 EMERGENT-2 trial evaluating the efficacy, safety, and tolerability the investigational agent xanomeline-trospium (KarXT) for adults with schizophrenia was announced by Karuna Therapeutics.¹

The trial met its primary endpoint: KarXT demonstrated 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 versus -11.6 placebo, p<0.0001) at week 5 (Cohen’s d effect size of 0.61). Starting at week 2, KarXT also demonstrated an early and sustained statistically significant reduction of symptoms, as assessed by PANSS total score. KarXT maintained this reduction through all timepoints in the trial.

“Despite the number of available treatment options, there continues to be a tremendous unmet need in the treatment of schizophrenia, placing an immense burden on both patients and their caregivers,” said Rishi Kakar, MD, chief scientific officer, Segal Trials and lead investigator of the phase 3 EMERGENT-2 trial. “These data build on the growing body of clinical evidence supporting the potential of KarXT as a new and differentiated approach for schizophrenia, demonstrating notable improvements across both positive and negative symptoms, while not being associated with common problematic side-effects of current therapies, such as weight gain, sedation, and movement disorders. This unique profile of KarXT has the potential to provide a new meaningful treatment option for our patients and their families beyond the current standard of care.”

KarXT also met key secondary endpoints, demonstrating a statistically significant reduction in both positive symptoms (eg, hallucinations or delusions) and negative symptoms (eg, difficulty enjoying life or withdrawal from others) of schizophrenia as measured by the PANSS positive (-6.8 KarXT versus -3.9 placebo, p<0.0001), PANSS negative (-3.4 KarXT versus -1.6 placebo, p=0.0055), and PANSS negative Marder factor subscales (-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% versus 21%). The overall treatment-emergent adverse events rate for KarXT and placebo was 75% and 58%, respectively. The most common treatment-emergent adverse events (>5%) in the KarXT arm were all mild to moderate in severity and included constipation, dyspepsia, nausea, vomiting, headache, increases in blood pressure, dizziness, gastroesophageal reflux disease (acid reflux), abdominal discomfort, and diarrhea.

“We are thrilled that these topline results from the Phase 3 EMERGENT-2 trial confirm what was seen in our Phase 2 EMERGENT-1 trial and underscore the potential for KarXT, with its novel and unique mechanism of action, to redefine what successful treatment looks like for the 21 million people living with schizophrenia worldwide, and potentially usher in the first new class of medicine for these patients in more than 50 years,” said Steve Paul, MD, chief executive officer, president and chairman of Karuna Therapeutics. “These results represent our second positive registrational trial. We look forward to continuing to gather long-term safety data to support our submission of a New Drug Application with the US Food and Drug Administration [FDA] for KarXT as a treatment for schizophrenia, which we expect to occur in mid-2023.”

To see more on KarXT, watch the video “Promising Publication: The Novel Schizophrenia Treatment Gaining Traction,” in which Stephen Brannan, MD, chief medical officer of Karuna Therapeutics, shared more information on the phase II clinical data.

Reference

1. Karuna Therapeutics announces positive results from phase 3 EMERGENT-2 Trial of KarXT in schizophrenia. Business Wire. August 8, 2022. https://www.businesswire.com/news/home/20220808005222/en/Karuna-Therapeutics-Announces-Positive-Results-from-Phase-3-EMERGENT-2-Trial-of-KarXT-in-Schizophrenia