FDA Accepts NDA, Grants PDUFA Date for Investigational Schizophrenia Treatment


The FDA’s decision is set for September 2024.



Karuna Therapeutics announced that the US Food & Drug Administration (FDA) has accepted its New Drug Application (NDA) for KarXT (xanomeline-trospium) for the treatment of schizophrenia in adults and granted a Prescription Drug User Fee Act (PDUFA) date of September 26, 2024.1

“We are pleased the NDA for KarXT has been accepted, and we look forward to working with the FDA during the review process,” said Bill Meury, president and chief executive officer at Karuna Therapeutics, in a press release. “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.”

Karuna’s NDA submission on September 28, 2023, was supported by comprehensive data on the safety and efficacy of KarXT derived from the EMERGENT program, a clinical initiative by Karuna Therapeutics aimed at assessing KarXT as a treatment for schizophrenia. The EMERGENT program includes a trio of successfully completed placebo-controlled trials—EMERGENT-1, EMERGENT-2, and EMERGENT-3—all of which systematically compared the efficacy and safety of KarXT to a placebo. Data on the long-term safety of KarXT from the ongoing EMERGENT-4 and EMERGENT-5 trials were also included in the NDA submission.2

In EMERGENT-1, EMERGENT-2, and EMERGENT-3, KarXT consistently achieved its primary objective, demonstrating a significant and clinically relevant reduction in the total score on the Positive and Negative Syndrome Scale (PANSS) when compared to placebo. KarXT also exhibited reductions in both positive and negative symptoms of schizophrenia, as assessed through the PANSS positive, PANSS negative, and PANSS negative Marder factor subscales—the secondary endpoints across all 3 trials.2

KarXT demonstrated good tolerability, and the most often reported adverse events included cholinergic characteristics and were categorized as mild to moderately severe. The rates of discontinuation due to treatment-related adverse events were low and showed similarity between KarXT and placebo in all trials. KarXT also did not exhibit the typical adverse events that are commonly associated with currently available antipsychotic medications, such as alterations in metabolic function, weight gain, drowsiness, and extrapyramidal symptoms.2

KarXT is an investigational muscarinic antipsychotic that functions as a dual M1/M4 muscarinic acetylcholine receptor agonist within the central nervous system. Research suggests that this may mediate cognitive, positive, and negative symptoms of schizophrenia. KarXT also does not directly block dopamine receptors, which differentiates it from existing treatments in this indication and positions the drug as a potential new approach to the treatment of schizophrenia.2

“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,” said Rishi Kakar, MD, chief scientific officer and medical director of Segal Trials, and investigator in the EMERGENT program, in a press release. “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.”

Stay up-to-date on news related to research on promising new treatments for schizophrenia and a wide variety of other psychiatric disorders at psychiatrictimes.com.

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


1. Karuna Therapeutics announces US Food and Drug Administration accepts New Drug Application for KarXT for the treatment of schizophrenia. Karuna Therapeutics. News release. November 29, 2023. Accessed November 30, 2023. https://investors.karunatx.com/news-releases/news-release-details/karuna-therapeutics-announces-us-food-and-drug-administration

2. O’Brien E. NDA submitted for investigational muscarinic antipsychotic in the treatment of schizophrenia. Psychiatric Times. September 28, 2023. Accessed November 30, 2023. https://www.psychiatrictimes.com/view/nda-submitted-for-investigational-muscarinic-antipsychotic-in-the-treatment-of-schizophrenia

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