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Supporting evidence for first-in-class novel schizophrenia therapy with digital cognitive endpoints

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Industry

Pharmaceutical

Challenge Summary

Cognitive impairment is a core feature of schizophrenia, yet treatment effects remain difficult to measure, stratify and replicate in clinical trials. Karuna Therapeutics (now part of Bristol Myers Squibb) sought to reliably evaluate the impact of KarXT, a novel muscarinic receptor therapy, on cognitive performance alongside symptom relief.

Solution Summary

A targeted CANTAB battery was deployed in Phase 3 trials to provide objective, standardised measurement of cognitive performance. Extensive normative data enabled identification of participants with baseline cognitive impairment, where treatment effects were detected and replicated, leading to the subsequent approval of this first-in-class therapy.

Key Product

Cognitive Assessments

www.cambridgecognition.com
307
participants completed
39%
participants with baseline cognitive impairment showed meaningful cognitive improvement
4
key cognitive domains assessed using CANTAB
First-in-class
schizophrenia monotherapy with demonstrated replicable cognitive benefits

The Challenge

Cognitive impairment is a core feature of schizophrenia and significantly affects daily functioning, independence, and quality of life. However, while many existing treatments address psychotic symptoms, efforts to develop therapies that improve cognitive functioning have largely been unsuccessful.

One major barrier has been the difficulty of accurately measuring cognition and replicating findings across clinical trials.

During the development of KarXT, a novel schizophrenia therapy combining xanomeline, a muscarinic receptor agonist, and trospium chloride, a peripherally restricted muscarinic receptor antagonist, Karuna Therapeutics (now part of Bristol Myers Squibb) sought to evaluate potential effects on cognitive function alongside symptom improvement.

The Solution

To provide objective and standardised measurement of cognition, Cambridge Cognition’s CANTAB digital cognitive assessments were implemented in the Phase 3 clinical trials.

Working with Cambridge Cognition’s experts, a targeted battery of tests was selected to measure cognitive domains commonly affected in schizophrenia.

The selected CANTAB tasks assessed four key domains:

  • One Touch Stockings of Cambridge (OTS): executive function, spatial planning and working memory
  • Spatial Span (SSP): short-term visual memory
  • Rapid Visual Information Processing (RVP): sustained attention and processing speed
  • Verbal Recognition Memory (VRM): verbal recall and recognition

This enabled researchers to collect standardised, quantitative cognitive data throughout the trial programme.

Results

307 participants completed CANTAB cognitive assessments across two Phase 3 trials

39% of participants with baseline cognitive impairment showed meaningful cognitive improvement

Four key cognitive domains assessed using CANTAB

First-in-class cognitive evidence

Collectively, the KarXT clinical studies represent the first time a schizophrenia monotherapy has demonstrated replicable cognitive benefits across both Phase 2 and Phase 3 trials.

From clinical trials to FDA approval

KarXT was subsequently approved by the U.S. Food and Drug Administration in 2024 under the brand name Cobenfy.

References

1.  Horan, William P., et al. "The Impact of Xanomeline and Trospium Chloride on Cognitive Impairment in Acute Schizophrenia: Replication in Pooled Data From Two Phase 3 Trials." American Journal of Psychiatry (2024).
2.  Kaul, Inder, et al. "Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline-trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial." The Lancet 403.10422 (2024): 160-170.