NDA for Investigational Schizophrenia Treatment Submitted to FDA

A New Drug Application (NDA) has been submitted to the US Food & Drug Administration (FDA) for an investigational muscarinic antipsychotic for the treatment of schizophrenia.

The NDA was submitted for investigational muscarinic antipsychotic, KarXT (xanomeline-trospium), which 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. The drug also does not block dopamine receptors directly, which differentiates it from existing treatments in this indication and positions the drug as a potential new approach to the treatment of schizophrenia.¹

“Schizophrenia is a serious mental illness that affects how one thinks, feels, and behaves, with symptoms often appearing in patients in early adulthood, during the prime years of their lives,” said Bill Meury, president and chief executive officer of KarXT developer Karuna Therapeutics, in a press release. “While current therapies have made a difference for many patients, they are not without limitations due to lack of full symptom relief or side effects that may lead to treatment discontinuation. KarXT, if approved, will represent the first novel pharmacological approach to treating schizophrenia in several decades and provide a new treatment option for patients and their physicians.”

The submission of the NDA was supported by comprehensive data on the effectiveness and safety of KarXT derived from the EMERGENT program, a clinical initiative by Karuna Therapeutics aimed at assessing KarXT as a potential treatment for schizophrenia. The EMERGENT program encompasses 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.¹

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.¹

KarXT demonstrated good tolerability overall, with the most frequently reported adverse events having cholinergic characteristics and being 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.¹

“The NDA submission represents an important step toward helping patients in need,” said Meury in a press release. “It is also a defining moment for Karuna Therapeutics. It represents the culmination of years of pre-clinical and clinical development, and a great deal of skill and hard work by our R&D organization. Our priorities over the next year are the regulatory review process, our ongoing development efforts, and building the platform to introduce KarXT to the medical community. I believe we are uniquely positioned to make a positive impact on how neuropsychiatric conditions are treated.”

Karuna Therapeutics has announced that, if KarXT is approved by the FDA for the treatment of schizophrenia following submission of the NDA, the drug will potentially be launched in the second half of 2024.²

This article was originally published on Psychiatric Times.

References

1. Karuna Therapeutics submits New Drug Application to US Food and Drug Administration for KarXT for the treatment of schizophrenia. Karuna Therapeutics. News release. September 28, 2023. Accessed September 28, 2023. https://investors.karunatx.com/news-releases/news-release-details/karuna-therapeutics-submits-new-drug-application-us-food-and

2. Karuna Therapeutics announces positive results from phase 3 EMERGENT-3 trial of KarXT in Schizophrenia. Karuna Therapeutics. March 20, 2023. Accessed September 28, 2023. https://investors.karunatx.com/news-releases/news-release-details/karuna-therapeutics-announces-positive-results-phase-3-0