Karuna Therapeutics Inc’s Xanomeline-trospium (KarXT) Was Clinically Meaningful and Statistically Significant on the Positive and Negative Syndrome Scale (PANSS) Total Score Compared to Placebo at Week 5 in Schizophrenia Patients showed a significant 8.4 point decrease.
In the EMERGENT-3 (NCT04738123) trial, xanomeline-trospium demonstrated early, sustained, and statistically significant symptom relief from week 2 through the end of the study, as assessed by the PANSS total score. This is consistent with previous trials.
“[Xanomeline-trospium] has now demonstrated robust and consistent symptom reduction in all three registry trials, [xanomeline-trospium] with schizophrenia. For the first time in decades, these data bring us one step closer to a therapeutic option that may offer a novel mechanism of action for treating schizophrenia.
“We look forward to working closely with the FDA and will keep our eyes on the regulatory process, including future pre-reviews.[new drug application (NDA) meeting in early second quarter, and remain on track for an NDA submission in mid-2023,” he said.
Additionally, xanomeline-trospium demonstrated a reduction in positive and negative symptoms of schizophrenia as measured by PANSS positive, PANSS negative, and PANSS negative Marder factor subscales, the secondary endpoints in the trial.
Further, it also demonstrated a clinically meaningful and statistically significant 3.5-point reduction in PANSS positive subscale compared with the placebo at week 5,
The treatment did not meet the threshold for statistical significance at week 5. However, xanomeline-trospium did demonstrate a statistically significant reduction in PANSS negative subscale and PANSS negative Marder factor subscale compared with the placebo at week 4.
“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,” David Walling, PhD, chief clinical officer at CenExel CNS and an investigator on the EMERGENT-3 trial, said in a statement.
“The results from the EMERGENT-3 trial add to the growing body of data which suggest [xanomeline-trospium] You can deal with schizophrenia symptoms without the common [adverse events (AEs)] We can see that with current treatment options,” he said.
Researchers found xanomeline-trospium to be generally well tolerated with a safety profile consistent with previous trials. The overall study discontinuation rate was 37% in the xanomeline-trospium group and 29% in the placebo group.
Overall treatment emergent AE (TEAE) rates for xanomeline-trospium and placebo were 70% and 50%, respectively. Discontinuation rates related to TEAEs were similar between treatment arms at 6% and 5%, respectively, which was consistent with previous trials.
The only serious TEAE reported in the xanomeline-trospium group was related to gastroesophageal reflux disease, which the researchers said was not related to xanomeline-trospium.
The most common TEAEs were constipation, diarrhea, dyspepsia, headache, hypertension, insomnia and nausea, all of which were mild or moderate.
The NDA submission for xanomeline-trospium in schizophrenia included long-term safety data from EMERGENT as well as efficacy from three trials: EMERGENT-1 (NCT03697252), EMERGENT-2 (NCT04659161), and EMERGENT-3. and safety data are included. -4 (NCT04659174) and EMERGENT-5 (NCT04820309).
Karuna Therapeutics plans to submit an NDA to the FDA in mid-2023 and, if approved, could launch in late 2024.
Karuna Therapeutics announced positive results from the Phase 3 EMERGENT-3 trial of KarXT in schizophrenia. Karuna Therapeutics. News Release. March 20, 2023. Accessed March 21, 2023. https://investors.karunatx.com/news-releases/news-release-details/karuna-therapeutics-announces-positive-results-phase-3-0