FDA Accepts New Drug Application for Novel Schizophrenia Treatment

The FDA has accepted a New Drug Application (NDA) for Karuna Therapeutics, Inc’s KarXT (xanomeline-trospium) treatment for schizophrenia in adult patients. The novel muscarinic antipsychotic is currently in development to treat schizophrenia and psychosis related to Alzheimer disease.¹

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“There is a significant need for new treatment options for serious mental illness. If approved, KarXT could be one of the more important new product introductions in neuropsychiatry by providing a novel pharmacological approach for the treatment of schizophrenia,” said Bill Meury, Karuna Therapeutics president and chief executive officer, said in a press release.¹

Schizophrenia can be a disabling condition, potentially causing a combination of hallucinations, delusions, and extremely disordered thinking and behavior that has a negative impact on the ability to function in daily life. As such, patients with schizophrenia require lifelong treatment; however, treatment initiated early after diagnosis may help to get the symptoms under control prior to the development of serious complications, which may improve long-term outlook for patients.²

Schizophrenia is estimated to affect approximately 0.3% of the global population and an estimated 2.8 million patients in the United States. The course of the condition is typically characterized by acute episodes of psychotic behaviors occurring at varying intervals between periods of relative symptomatic stability.

Its characteristics are classified as positive symptoms (hallucinations and delusions), negative symptoms (difficulties enjoying life and social withdrawal), and cognitive impairment (inhibited memory, concentration, and decision-making). Despite advancements in managing the symptoms of the condition, approximately 30% of patients do not improve with therapy, and 50% experience a partial improvement in symptoms.

KarXT has a novel mechanism of action that acts as a dual M1/M4 muscarinic acetylcholine receptor agonist in the central nervous system. Karuna stated the therapy is believed to produce improvements in the positive, negative, and cognitive symptoms of schizophrenia. The therapy may offer an alternative approach to treating schizophrenia because it does not directly block dopamine receptors.¹

The submission of the NDA was supported by data from the EMERGENT clinical program evaluating KarXT as a treatment for schizophrenia, which demonstrated the drug’s efficacy and long-term safety, according to Karuna. Across all three placebo-controlled trials in the EMERGENT program, the drug achieved the primary endpoint of statistically significant and clinically meaningful improvements in the symptoms of schizophrenia vs. placebo as measured by Positive and Negative Syndrome Scale (PANSS) total score.

In terms of safety, KarXT was generally well tolerated, with the most common adverse events (AEs) being cholinergic in nature and mild to moderate in severity. Significantly, the drug was not associated with the AEs that are common among currently available antipsychotics, such as weight gain, somnolence, and movement disorders.

“KarXT focuses on a novel pathway through muscarinic receptors to indirectly modulate dopamine signaling in key brain circuits, and in clinical trials completed to date KarXT has demonstrated the much-needed combination of strong tolerability and clinically meaningful symptom reduction,” EMERGENT program investigator Rishi Kakar, MD, chief scientific officer and medical director of Segal Trials, said in a press release.¹ “This decision by the FDA marks an important step in working toward a new chapter in the standard of care for those facing the immense, daily struggle of this serious mental illness.”

The application has been granted a Prescription Drug User Fee Act date of September 26, 2024.

References

1. Karuna Therapeutics Announces U.S. Food and Drug Administration Accepts New Drug Application for KarXT for the Treatment of Schizophrenia. Karuna Therapeutics. November 29, 2023. https://investors.karunatx.com/news-releases/news-release-details/karuna-therapeutics-announces-us-food-and-drug-administration. Accessed November 29, 2023.

2. Schizophrenia. Mayo Clinic. Webpage. Updated January 7, 2020. Accessed November 29, 2023. https://www.mayoclinic.org/diseases-conditions/schizophrenia/symptoms-causes/syc-20354443