| Clinical data | |
|---|---|
| Other names | HTL-0016878; NBI-1117568; NBI-568 |
| Routes of administration | Oral |
| Drug class | Muscarinic acetylcholine M4 receptor agonist |
NBI-1117568 (former developmental code name HTL-0016878) is an investigational antipsychotic drug for schizophrenia [1] that was out-licensed Nexera Pharma in to Neurocrine Biosciences, a United States-based pharmaceutical company. [2] [3] It is administered orally. [4] [5]
It is a selective muscarinic acetylcholine M4 receptor agonist that indirectly modulates dopamine as the basis for its putative improvement of schizophrenia. [4] In April 2016, the compound was out-licensed to Allergan, an Irish pharmaceutical company. By September 2017, it had advanced to Phase I clinical trial for the indication of "neuropsychiatric symptoms associated with Alzheimer's disease and other dementias" [6] However, in May 2020, Allergan was acquired by AbbVie, and due to AbbVie's pipeline business decisions, the license was returned to Nexceris in January 2021. [7] In November 2021, the compound was newly out-licensed to Neurocrine Biosciences, a U.S. pharmaceutical company. [3] It has been under development as a treatment for schizophrenia, and as of September 2024, Phase II clinical trials have been completed. [8] [9]
The Phase II clinical trial was conducted in 15 sites across the U.S. with 200 adult patients diagnosed with schizophrenia. [12] The primary endpoint was assessed by the change in the total score of the Positive and Negative Syndrome Scale (PANSS) after six weeks of treatment. The 20 mg once-daily group showed a statistically significant improvement of 7.5 points compared to the placebo group (improvement of 18.2 points from baseline, p = 0.011, effect size = 0.61). [13] However, the 40 mg once-daily group, 60 mg once-daily group, and 30 mg twice-daily group did not show statistically significant differences compared to the placebo group (p-values: 40 mg group: 0.282, 60 mg group: 0.189, 30 mg twice-daily group: 0.090). [13]
With a PANSS improvement of 7.5, NBI-111758 lagged behind xanomeline/trospium (KarXT) (Karuna Therapeutics) with 8.4 and emraclidine (Cerevel Therapeutics) with 12.7, both of which were in clinical trials at the same time. Moreover, the lack of dose-dependency led to disappointment in the stock market. [14] Neurocrine Biosciences' share price dropped 19% on the day following the announcement of the Phase II clinical trial results. [15]