Positive Top-line Phase 2 Results for Novel Agent in Acute Psychosis

Megan Brooks

November 18, 2019

KarXT (Karuna Therapeutics) met its primary endpoint in a phase 2 clinical trial of acute psychosis in patients with schizophrenia, the company has announced.

KarXT is an oral coformulation of xanomeline, a novel muscarinic receptor agonist, and trospium, an approved muscarinic receptor antagonist. It is designed to treat psychosis and related symptoms through preferential stimulation of muscarinic receptors in the central nervous system (CNS).

The phase 2 study was a randomized, double-blind, placebo-controlled trial involving 182 adult patients with schizophrenia who were experiencing acute psychosis.

Patients were washed-out of antipsychotic medicines and randomized to receive either KarXT or placebo for 5 weeks. The primary outcome measure of the trial was the change from baseline on the total Positive and Negative Syndrome Scale (PANSS) score with KarXT vs placebo at week 5.

KarXT demonstrated a statistically "significant and clinically meaningful" 11.6 point average reduction in total PANSS score compared with placebo (P < .0001), the company reports. KarXT also led to a statistically significant reduction in the secondary endpoints of PANSS-Positive and PANSS-Negative scores (P < .001).

KarXT was well tolerated, with similar discontinuation rates of patients on KarXT (20%) and placebo (21%). The number of discontinuations due to treatment-emergent adverse events were equal in the KarXT and placebo groups (2 in each group).

The most common adverse events were constipation, nausea, dry mouth, dyspepsia, and vomiting. Occurrences of somnolence, weight gain, and extrapyramidal symptoms were similar to placebo. One serious adverse event was experienced in the KarXT treatment group, in which the patient discontinued treatment and subsequently sought hospital care for worsening psychosis.

"The results of the Phase 2 trial are impressive and encouraging because they indicate that KarXT, if approved, could represent a game-changing therapeutic advance in the treatment of patients with schizophrenia," Jeffrey Lieberman, MD, professor and chairman, Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York City, said in the release.

"The effectiveness of antipsychotics has been limited by the frequent and serious side effects of first- and second-generation drugs, which are difficult for many patients to tolerate, are potentially harmful, and lead to high rates of discontinuation and relapse," added Lieberman, a member of Karuna's scientific advisory board.

"In addition to its novel mechanism of action, KarXT could be a new therapeutic option that has the potential to offer robust efficacy devoid of weight gain, metabolic effects, and extrapyramidal side effects," he said.

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