Karuna Therapeutics Announces Topline Results from Schizophrenia Therapy Clinical Trial

On August 8, Karuna Therapeutics shared that its lead investigational therapy, KarXT (xanomeline-trospium), yielded topline results in its Phase 3 clinical trial. The trial evaluated the treatment’s efficacy, safety, and tolerability in adults with schizophrenia.

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KarXT, An Alternative Schizophrenia Therapy

KarXT is an M1/M4-preferring muscarinic agonist designed to treat conditions including schizophrenia and psychosis in Alzheimer’s. 

Schizophrenia has two kinds of symptoms: positive symptoms and negative symptoms. Positive symptoms include hallucinations and delusions, while negative symptoms include difficulty enjoying life and withdrawal from others. KarXT treats both through preferential stimulation of the patient’s muscarinic receptors in the central nervous system. 

Unlike other treatments for severe mental illness, KarXT does not rely on releasing dopamine or serotonin for treatment. This would make KarXT the first of a new kind of medicine with the potential to revolutionize schizophrenia therapy, should it be approved. 

Results from the Phase 3 EMERGENT-2 trial

The Phase 3 EMERGENT-2 trial evaluates the efficacy, safety, and tolerability of KarXT in adults with schizophrenia. It is a double-blind, placebo-controlled, five-week, inpatient trial. The trial’s primary endpoint was a change in baseline in the Positive and Negative Syndrome Scale (PANSS) total score. This is a scale measuring the severity of schizophrenia symptoms. 

Two hundred fifty-two adults diagnosed with schizophrenia enrolled in the trial, half receiving KarXT and the other half receiving a placebo. After five weeks of administering the treatment, researchers noted a 2.9-point reduction in PANSS positive symptoms with KarXT compared to the placebo. In addition, they saw a 1.8-point decrease in the PANSS scale for negative symptoms with KarXT compared to the placebo. On top of that, patients found KarXT to be tolerable. 

On the findings, Steve Paul, M.D., chief executive officer, president, and chairman of Karuna Therapeutics, said, “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, to redefine what successful treatment looks like.”

The completion of the Phase 3 EMERGENT-2 marks another positive win for the EMERGENT program. Aside from the completed Phase 2 EMERGENT-1 and Phase 3 EMERGENT-2 trials, the program has three other ongoing trials. EMERGENT-3, EMERGENT-4, and EMERGENT-5 are currently evaluating the acute efficacy and long-term safety of KarXT.

Karuna Therapeutics plans to use the data from the EMERGENT program to support an application for an NDA with the United States Food and Drug Administration (FDA) for KarXT as a schizophrenia therapy. They expect to submit this application by mid-2023, when all the EMERGENT trials have concluded.

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Author

Max Heirich