Karuna’s KarXT Aces Third Registrational Study in Schizophrenia

Photo shows researchers looking at brain scans/Getty Images

Photo shows researchers looking at brain scans/Getty Images

Karuna Therapeutics is three for three in its quest to bring a novel schizophrenia treatment to the market. Data released Monday from the Phase III EMERGENT-3 trial show KarXT (xanomeline-trospium) met its primary endpoint, inducing a significant and clinically meaningful improvement in symptom severity.

After five weeks of treatment, patients in the KarXT arm scored 20.6 points lower on the Positive and Negative Syndrome Scale (PANSS), a validated scale for measuring the severity of schizophrenia symptoms. Placebo comparators, on the other hand, saw a score reduction of 12.2 points relative to baseline.

The between-group difference of 8.4 points proved to be statistically significant and clinically meaningful, according to the press release.

KarXT also induced significant improvements in the positive and negative symptoms of schizophrenia, as assessed by the respective PANSS subscales.

These beneficial effects were apparent as early as two weeks after initiating KarXT treatment and persisted until the end of the study.

EMERGENT-3 is a double-blinded and placebo-controlled study evaluating the therapeutic potential of KarXT in 256 adult schizophrenia patients who were experiencing symptoms of psychosis. Aside from efficacy, the trial also looked at safety and found the candidate to be generally well-tolerated.

In the KarXT and placebo arms, the rates of treatment-emergent adverse events were 70% and 50%, respectively, while 6% and 5% of patients in the respective groups dropped out of the study due to these toxicities.

“The results mark our third positive trial of KarXT in schizophrenia, further reinforcing the clear, consistent efficacy, safety and tolerability results seen in our prior trials,” Bill Meury, president and CEO, Karuna, said in an investor call Monday morning.

Meury said the results hold promise for a novel and needed new treatment option.

If approved, KarXT would be the first therapy to treat the negative symptoms of schizophrenia.

Looking Ahead to Launch

With data from EMERGENT-3 in hand and positive results from two previous studies, Karuna intends to submit a New Drug Application for KarXT to the FDA by mid-2023, Meury said during the call. If approved, the company plans to launch the treatment during the second half of 2024.

In February 2021, Karuna published data from the Phase II registrational study EMERGENT-1 in The New England Journal of Medicine, showing that KarXT, given twice-daily over five weeks, elicited an 11.6-point drop in PANSS score relative to placebo.

Positive and negative schizophrenia symptoms, as well as clinician-rated disease severity, were likewise significantly improved after KarXT treatment.

In August 2022, Karuna released data from a third registrational study, the Phase III EMERGENT-2 trial. As in EMERGENT-1 and EMERGENT-3, twice-a-day and flexible dosing regimens of KarXT reduced PANSS score by nearly 10 points more than placebo after five weeks.  

Karuna is also currently running the Phase III EMERGENT-4 and EMERGENT-5 trials, both of which are examining the long-term safety and efficacy of KarXT.

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