FDA Accepts Xanomeline-Trospium Drug Application for Schizophrenia Treatment

Karuna Therapeutics announced today the Food and Drug Administration (FDA) accepted its xanomeline-trospium (KarXT) New Drug Application for the treatment of adults with schizophrenia.¹

“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, president and chief executive officer of Karuna Therapeutics in a press release.

Schizophrenia affects 2.8 million in the US and hinders daily living. Characteristics of the mental illness fall into 3 domains: positive symptoms (hallucinations and delusions), negative symptoms (struggle with enjoying life and withdrawal from others), and cognitive impairment (issues in memory, concentration, and decision-making). People with schizophrenia struggle to keep jobs, live independently, and to maintain relationships. Although current schizophrenia treatment can be effective in managing symptoms, about 30% do not have improvements after therapy, and 50% only have partial improvements in symptoms.

Xanomeline-trospium acts as a dual M1/M4 muscarinic acetylcholine receptor agonist in the central nervous system, believing to help positive, negative, and cognitive symptoms of schizophrenia. While other treatments of schizophrenia directly block dopamine receptors, this drug does not, offering a new approach to treating the mental illness.

If the FDA approves xanomeline-trospium, it will mark as the first pharmacological approach to treating schizophrenia since the 1970s. Within the past year, the FDA approved a New Drug Application for aripiprazole, a bi-monthly injection, that treats schizophrenia and bipolar disorder.² Though xanomeline-trospium shows promise through the pivotal EMERGENT trial, demonstrating how xanomeline-trospium is associated with significant improvements in schizophrenia symptoms.¹

The EMERGENT program included 5 trials. The first 3 trials compared xanomeline-trospium with a placebo to access efficacy and safety, and 2 trials evaluating the long-term safety of the drug.

In the 3 placebo-controlled trials, xanomeline-trospium demonstrated statistically significant improvements in schizophrenia symptoms compared to placebo. Also, the drug was typically well-tolerated—the only adverse events were cholinergic and mild to moderate in severity. Unlike other antipsychotics, xanomeline-trospium was not associated with weight gain, somnolence, and movement disorders.

“Diagnosis marks the beginning of an often long and tiresome search for effective and tolerable treatment options,” said Gordon Lavigne, M.Ed., chief executive officer of Schizophrenia & Psychosis Action Alliance, in a Karuna Therapeutics press release. “The nature and magnitude of side effects often play a pivotal role in whether someone continues treatment, which is often crucial to minimize the risk of relapse and realize the life-altering benefits of long-term treatment. Potential approval of a pharmacologically distinct treatment option would be a welcome innovation for people living with schizophrenia.”

The FDA will decide on the approval of xanomeline-trospium for the treatment of schizophrenia patients by 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. ^{Kunzmann, K. FDA Approves Bi-Monthly Aripiprazole Injection for Schizophrenia, Bipolar Disorder. April 28, 2023. https://www.hcplive.com/view/fda-approves-aripiprazole-injection-schizophrenia-bipolar-disorder. Accessed November 29, 2023.}