Following the success of the phase 3 EMERGENT-2 trial, researchers suggest that xanomeline-trospium could be a safe and effective treatment option for adults with schizophrenia.
Xanomeline-trospium (KarXT; Karuna), an investigational drug for adults with schizophrenia, was found to be effective, safe, and tolerable, according to results from the phase 3 EMERGENT-2 trial.
The phase 3 EMERGENT-2 trial used the Positive and Negative Syndrome Scale (PANSS)—which measures the severity of schizophrenia symptoms—to assess the primary endpoint. The primary endpoint evaluated the ability of xanomeline-trospium to changethe PANSS total score from baseline after 5 weeks compared with placebo. Key secondary endpoints were baseline changes in PANSS positive, PANSS negative, and PANSS negative Marder factor subscale.
“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,” said Steve Paul, MD, chief executive officer, president and chairman of Karuna Therapeutics, in a press release.
At week 5, xanomeline-trospium showed a statistically significant and clinically meaningful drop on the PANSS scale (9.6 points), meeting the primary endpoint. The EMERGENT-2 trial met its key secondary endpoints as well, including a reduction in schizophrenia positive symptoms such as hallucinations (2.9 points), schizophrenia negative symptoms such as social isolation (1.8 points), and Marder factor subscale (2.2 points) compared to the placebo.
“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 for KarXT as a treatment for schizophrenia, which we expect to occur in mid-2023,” Paul said in the press release.
This EMERGENT program is evaluating the efficacy and long-term safety of xanomeline-trospium, an investigational M1/M4 muscarinic agonist designed to treat psychiatric and neurological conditions.
For this double-blind, placebo-controlled, 5-week trial, researchers randomized (1:1) 252 adults with diagnosed schizophrenia who had symptoms of psychosis. Patients either received xanomeline-trospium twice-daily (BID) or BID placebo.
The doses increased on days 1-2, day 3, and day 8. On day 8, patients were administered 125 mg of xanomeline and 30 mg trospium (125/30), the highest dose of xanomeline-trospium (or equivalent dose of placebo), and most patients took this dose for the rest of the trial.
This drug was well tolerated, and 5% or more of patients experienced mild and moderate adverse events, including constipation, dyspepsia, nausea, vomiting, headache, increased blood pressure, dizziness, gastroesophageal reflux disease, abdominal discomfort, and diarrhea.
“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,” said lead researcher Rishi Kakar, MD, chief scientific officer, Segal Trials, in the press release.
The findings from this trial are expected to warrant a new drug application submission to the FDA in 2023.
Karuna Therapeutics, Inc. Karuna Therapeutics Announces Positive Results from Phase 3 EMERGENT-2 Trial of KarXT in Schizophrenia. Karuna website. August 8, 2022. Accessed on September 20, 2022.