Schizophrenia Treatment KarXT Meets Primary Endpoint in Phase 3 Trial

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Xanomeline-trospium (KarXT) from Karuna Therapeutics Inc demonstrated a clinically meaningful and statistically significant 8.4-point reduction in the Positive and Negative Syndrome Scale (PANSS) total score compared with the placebo at week 5 for individuals with schizophrenia.

In the EMERGENT-3 (NCT04738123) trial, xanomeline-trospium demonstrated an early and sustained statistically significant reduction of symptoms from week 2 through the end of the trial as assessed by PANSS total score, which is consistent with prior trials.

“[Xanomeline-trospium] has now demonstrated a robust and consistent reduction of symptoms across all 3 registrational trials, providing a compelling picture of the potential of [xanomeline-trospium] in schizophrenia. With these data, we are 1 step closer to a potential treatment option that could provide the first new mechanism of action to treat schizophrenia in several decades,” Bill Meury, CEO and president of Karuna Therapeutics, said in a statement.

“We look forward to working closely with the FDA as we focus our attention on the regulatory process, including our upcoming pre-[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] could address the symptoms of schizophrenia without the common [adverse events (AEs)] we see with current treatment options,” he said.

Investigators found that xanomeline-trospium was generally well tolerated with a safety profile that was consistent with prior trials. The overall discontinuation rate in the trial was 37% for the xanomeline-trospium arm and 29% for the placebo arm.

The overall treatment emergent AE (TEAE) rates for xanomeline-trospium and the 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 arm was related to gastroesophageal reflux disease, which investigators said was not related to xanomeline-trospium.

The most common TEAEs were constipation, diarrhea, dyspepsia, headache, hypertension, insomnia, and nausea, which were all mild or moderate in severity.

The NDA submission for xanomeline-trospium in schizophrenia will incorporate the efficacy and safety data from the 3 trials, EMERGENT-1 (NCT03697252), EMERGENT-2 (NCT04659161), and EMERGENT-3, in addition to long-term safety data from EMERGENT-4 (NCT04659174) and EMERGENT-5 (NCT04820309).

Karuna Therapeutics plans to submit an NDA to the FDA in mid-2023, with a potential launch in the second half of 2024, if approved.

Reference

Karuna Therapeutics announces positive results from 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