Positive results from phase III EMERGENT-3 trial of KarXT in schizophrenia.- Karuna Therapeuticws Inc.
Karuna Therapeutics, Inc. announced positive topline results from its Phase III EMERGENT-3 trial evaluating the efficacy, safety, and tolerability of its lead investigational therapy, KarXT (xanomeline-trospium) in adults with schizophrenia.
The trial met its primary endpoint, with KarXT demonstrating a statistically significant and clinically meaningful 8.4-point reduction in Positive and Negative Syndrome Scale (PANSS) total score compared to placebo (-20.6 KarXT vs. -12.2 placebo; p<0.0001) at week 5 (cohen’s d effect size of 0.60). consistent with prior trials, karxt demonstrated an early and sustained statistically significant reduction of symptoms from week 2 (p><0.05) through the end of the trial as assessed by panss total score.></0.05)></0.0001)>
“Schizophrenia is a persistent and disabling condition that presents with symptoms which are often difficult to treat and manage. Despite the number of currently available treatments, there remains a significant need for new treatment options for the 21 million people living worldwide with schizophrenia,” said David Walling, Ph.D., chief clinical officer at Cenexel - CNS and investigator on the EMERGENT-3 trial. “The results from the EMERGENT-3 trial add to the growing body of data which suggest KarXT could address the symptoms of schizophrenia without the common side effects we see with current treatment options.”
KarXT also demonstrated reductions in positive and negative symptoms of schizophrenia as measured by PANSS positive, PANSS negative, and PANSS negative Marder factor subscales – secondary endpoints in the trial. KarXT demonstrated a clinically meaningful and statistically significant 3.5-point reduction in PANSS positive subscale compared to placebo at Week 5 (-7.1 KarXT vs. -3.6 placebo; p<0.0001). while not meeting the threshold for statistical significance at week 5, karxt did demonstrate a statistically significant reduction in panss negative subscale and panss negative marder factor subscale compared to placebo at week 4 (p><0.05).></0.05).></0.0001).>
KarXT was generally well tolerated, with a side effect profile substantially consistent with prior trials of KarXT. The overall discontinuation rate in the trial was 33% (37% KarXT vs. 29% placebo). The overall treatment emergent adverse event (TEAE) rates for KarXT and placebo were 70% and 50%, respectively. Discontinuation rates related to TEAEs were similar between treatment arms (6% KarXT vs. 5% placebo), consistent with the EMERGENT-1 and EMERGENT-2 trials.
The only serious TEAE reported in the KarXT arm was related to gastroesophageal reflux disease (acid reflux) and deemed not to be related to study drug. There were no serious TEAEs reported in the placebo group.
The most common KarXT TEAEs ( greater than 5%) were nausea, dyspepsia, vomiting, constipation, headache, hypertension, diarrhea, and insomnia, which were all rated mild or moderate in severity. There were no discontinuations due to TEAEs of hypertension. Mean blood pressure measures were similar between KarXT and placebo, and no syncopal events were observed. Similar to prior trials, an increase in heart rate was associated with KarXT treatment and decreased in magnitude by the end of the trial. Measures of weight gain, somnolence, and extrapyramidal symptoms of KarXT were similar to placebo, consistent with prior trials of KarXT in schizophrenia.
The NDA submission for KarXT in schizophrenia will incorporate the efficacy and safety data from the three placebo-controlled registrational trials, EMERGENT-1, EMERGENT-2, and EMERGENT-3, in addition to long-term safety data from the ongoing EMERGENT-4 and EMERGENT-5 trials. The Company is on track to submit an NDA to the FDA in mid-2023, with a potential launch in the second half of 2024, if approved.