Post Hoc Analysis Explores Risk-Benefit Profile of KarXT

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CONFERENCE REPORTER

A poster at the 2024 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting discussed a post hoc analysis of 3 phase 2 and 3 clinical trials analyzing the efficacy of KarXT, an investigational combination of xanomeline and trospium chloride, for the treatment of schizophrenia in adults.¹

The analysis presented in the poster incorporated data from 3 randomized, double-blind, placebo-controlled studies (NCT03697252,² NCT04659161,³ and NCT04738123⁴) involving adult patients. Researchers assessed the efficacy of KarXT using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impressions-Severity (CGI-S) score. They also evaluated the tolerability of the treatment by monitoring adverse effects, discontinuation rates due to adverse effects, and changes in metabolic and cardiac parameters.¹

According to the results,KarXT effectively reduces schizophrenia symptoms with a relatively favorable adverse effect profile. KarXT showed robust efficacy, with a number needed to treat (NNT) as low as 5 for a ≥ 20% reduction in PANSS scores. Other notable efficacy outcomes included NNT values of 5 for a ≥ 30% reduction in PANSS scores, 8 for a ≥ 40% reduction in PANSS scores, and 8 for achieving a CGI-S score of ≤ 3.¹

The treatment was associated with gastrointestinal adverse effects, such as nausea (NNH = 7) and vomiting (NNH = 9). However, the likelihood of discontinuation due to these adverse effects was relatively low (NNH = 49). KarXT also did not significantly affect weight gain or cause somnolence, unlike many existing antipsychotic medications.¹

The likelihood to be helped or harmed (LHH) for KarXT was greater than 1 for all efficacy outcomes compared with the harms, indicating that patients are more likely to experience therapeutic benefits than adverse events. For instance, the LHH for treatment response versus discontinuation due to adverse events was 21.8, and for response versus discontinuation due to gastrointestinal issues, it was 9.8.¹

According to the investigators, indirect comparisons with other first-line antipsychotics suggest that KarXT has a competitive edge, particularly in its minimal impact on weight gain and lower incidence of sedation. These attributes position KarXT as a potentially more tolerable option for patients who are sensitive to these common adverse effects of antipsychotic therapy.¹

The investigators concluded that KarXT shows significant promise as a treatment for schizophrenia, offering efficacy comparable to or exceeding that of existing first-line medications while exhibiting a favorable tolerability profile.¹

Although head-to-head trials with other antipsychotics are needed for more definitive comparisons, current evidence suggests that KarXT could provide a valuable alternative for managing schizophrenia, particularly for patients who experience significant adverse effects from other treatments. As research progresses, the investigators added, further studies will be essential to confirm these findings and establish the long-term safety and efficacy of KarXT in broader patient populations.¹

The US Food and Drug Administration is set to announce its decision on the approval of KarXT on September 26, 2024.⁵

The poster was presented by study co-author Nichole Neugebauer, PhD, of KarXT developer Karuna Therapeutics.

Are you interested in learning more about KarXT? Here are some of the latest updates on the treatment as seen in Psychiatric Times®:

The Latest Updates on KarXT

New Data Demonstrates KarXT’s Positive Long-Term Metabolic Profile

Changing the Way Schizophrenia Is Treated

“A New and Differentiated Approach for Schizophrenia”: Positive Results for Phase 3 Trial

Stay up-to-date on news related to research on promising new interventions and developments in the treatment of a wide variety of psychiatric disorders at psychiatrictimes.com.

Note: This article was prepared with the assistance of ChatGPT.

References

1. Kozauer SG, Durgam S, Earley WR, et al. KarXT (xanomeline and trospium) for the treatment of schizophrenia: number needed to treat, number needed to harm, and likelihood to be helped or harmed. American Society of Clinical Psychopharmacology Annual Meeting. Poster presentation. May 30, 2024. Accessed May 30, 2024.

2. A study to assess safety and efficacy of KarXT in adult patients with schizophrenia (EMERGENT-1). ClinicalTrials.gov. Last updated October 26, 2020. Accessed May 30, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT03697252

3. A study to assess efficacy and safety of KarXT in acutely psychotic hospitalized adult patients with schizophrenia (EMERGENT-2). ClinicalTrials.gov. Last updated December 12, 2023. Accessed May 30, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT04659161

4. A study to assess efficacy and safety of KarXT in acutely psychotic hospitalized adult patients with schizophrenia (EMERGENT-3). ClinicalTrials.gov. Last updated October 31, 2023. Accessed May 30, 2024. https://clinicaltrials.gov/study/NCT04738123

5. Kuntz L. New data demonstrates KarXT’s positive long-term metabolic profile. Psychiatric Times. April 12, 2024. Accessed May 30, 2024. https://www.psychiatrictimes.com/view/new-data-demonstrates-karxt-positive-long-term-metabolic-profile