NBI-1117568 (former developmental code name HTL-0016878) is an investigational antipsychotic drug for schizophrenia that was out-licensed Nexera Pharma in to Neurocrine Biosciences, a United States-based pharmaceutical company. It is administered orally.
Overview.
It is a selective muscarinic acetylcholine M4 receptor agonist that indirectly modulates dopamine as the basis for its putative improvement of schizophrenia. 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" 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. In November 2021, the compound was newly out-licensed to Neurocrine Biosciences, a U.S. pharmaceutical company. It has been under development as a treatment for schizophrenia, and as of September 2024, Phase II clinical trials have been completed.
Clinical trials.
Phase II clinical trial.
The Phase II clinical trial was conducted in 15 sites across the U.S. with 200 adult patients diagnosed with schizophrenia. 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). 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).
Market reaction to phase II clinical trial.
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. Neurocrine Biosciences' share price dropped 19% on the day following the announcement of the Phase II clinical trial results.