KARXT represents an investigational medication generating considerable interest within the medical community. This novel therapy is being explored for its potential in treating serious neurological conditions, particularly schizophrenia. KARXT highlights its potential to offer a new approach to managing symptoms for individuals living with these challenging disorders.
What is KARXT?
KARXT, known scientifically as xanomeline-trospium, is a unique medication designed to treat schizophrenia and potentially other psychotic disorders. Unlike many existing treatments that primarily affect dopamine receptors in the brain, KARXT operates through a different mechanism. It targets muscarinic acetylcholine receptors, specifically activating M1 and M4 receptors, which are found in various brain regions. This distinct approach aims to address symptoms of psychosis without some of the common side effects associated with traditional antipsychotics.
The drug combines xanomeline, a muscarinic receptor agonist, with trospium chloride, a peripheral muscarinic receptor antagonist. Trospium chloride is included to reduce unwanted side effects that might occur if xanomeline were to act on muscarinic receptors outside of the brain. This combination allows for the therapeutic effects of xanomeline while minimizing peripheral adverse events, making KARXT a potentially well-tolerated option for patients.
Key Clinical Trial Discoveries
Recent clinical trials have provided significant insights into KARXT’s efficacy and safety profile. The Phase 3 EMERGENT-2 trial, a randomized, double-blind, placebo-controlled study, enrolled 252 adults with schizophrenia experiencing acute psychosis. This trial demonstrated a statistically significant and clinically meaningful reduction in the Positive and Negative Syndrome Scale (PANSS) total score, with a 9.6-point improvement for KARXT compared to placebo at week 5. The improvement in symptoms was observed as early as week 2.
KARXT also met its key secondary endpoints, showing significant reductions in both positive symptoms, such as hallucinations and delusions, and negative symptoms, like social withdrawal or lack of motivation. Specifically, there was a 2.9-point reduction in the PANSS positive subscale and a 1.8-point reduction in the PANSS negative subscale compared to placebo. The EMERGENT-3 trial further supported these findings, consistently demonstrating KARXT’s efficacy and good tolerability.
Common side effects observed with KARXT included constipation, nausea, vomiting, dyspepsia, and hypertension, generally mild to moderate in severity and often transient. Importantly, KARXT was not associated with common side effects of current antipsychotics, such as weight gain, sedation, or movement disorders.
Current Regulatory Path and Next Steps
KARXT is currently navigating the regulatory pathway toward potential approval. Karuna Therapeutics submitted a New Drug Application (NDA) for KARXT for the treatment of schizophrenia in adults to the U.S. Food and Drug Administration (FDA) in September 2023. The FDA accepted this application and has assigned a Prescription Drug User Fee Act (PDUFA) date of September 26, 2024. This PDUFA date indicates the target date by which the FDA aims to make a decision on the approval of the drug.
The NDA submission was supported by comprehensive data from the EMERGENT clinical program, including the EMERGENT-1, EMERGENT-2, and EMERGENT-3 trials. The FDA’s review process involves a thorough evaluation of the submitted data on the drug’s safety and efficacy. The regulatory decision on or before the PDUFA date will determine the future availability of KARXT to patients.
Potential Impact on Treatment
The potential approval of KARXT could represent a significant advancement in the treatment of schizophrenia. If approved, it would be the first new class of antipsychotic medication with a novel mechanism of action in several decades, offering an alternative to existing dopamine-receptor blocking agents. This new approach could be particularly beneficial for individuals who have not responded well to current treatments or who experience burdensome side effects from them.
KARXT’s distinct tolerability profile, notably its lack of association with weight gain, sedation, and extrapyramidal symptoms often seen with other antipsychotics, could improve treatment adherence and overall patient quality of life. The availability of a treatment that addresses both positive and negative symptoms with a different side effect profile could offer new hope and broader treatment options for patients, their caregivers, and the broader medical community.