Tardive Dyskinesia

October 26, 2015

Neurocrine Biosciences has issued results of a phase III study of NBI-98854 for moderate to severe tardive dyskinesia patients with underlying schizophrenia, schizoaffective disorder, bipolar or major depressive disorder. The Kinect 3 study was a randomized, parallel-group, double-blind, placebo-controlled trial and randomized 234 subjects to either placebo, once-daily 40mg of NBI-98854 or once-daily 80mg of NBI-98854 for six weeks. Subsequent to the completion of the six-week, placebo-controlled dosing, all subjects are placed on once-daily 40mg or once-daily 80mg of NBI-98854 through week 48. The pre-specified primary efficacy endpoint was the change from baseline in the Abnormal Involuntary Movement Scale (AIMS) at week six in the 80mg once-daily dosing group compared to placebo as assessed by central blinded video raters. The AIMS ratings at week six for the 80mg once-daily NBI-98854 intention-to-treat population was reduced 3.1 points (Least-Squares Mean) more than placebo (p<0.0001). NBI-98854 was generally well-tolerated. The frequency of adverse events was similar among all treatment groups and treatment emergent adverse effects were consistent with those of prior studies. In addition to Kinect 3, a separate one-year open-label safety study of NBI-98854, Kinect 4, also has been initiated to support the anticipated 2016 filing of a NDA in tardive dyskinesia anticipated to be filed in 2016.

January 20, 2014

Neurocrine Biosciences issued results of a phase IIb study of NBI-98854. The randomized, parallel, double-blind, placebo-controlled, dose-titration trial utilized the capsule formulation in moderate to severe tardive dyskinesia patients with an underlying mood disorder, schizophrenia or schizoaffective disorder, or a gastrointestinal disorder with exposure to metoclopramide. This 100-subject study assessed once-daily NBI-98854 over a six-week placebo-controlled dosing period. The dosing regimen began with a once-daily dose of 25mg for the initial two weeks before patients were titrated to a once-daily 50mg dose, or continued on the once-daily 25mg dose for the following two-week period. At the completion of the second two weeks of treatment, patients were eligible to be titrated to a once-daily 75mg, 50mg or 25mg dose for the final two weeks of treatment. At week 6, the Abnormal Involuntary Movement Scale (AIMS) scores were reduced by 2.6 points in the NBI-98854 intention-to-treat (ITT) group compared to a reduction of 0.2 points in the placebo arm (p<0.001). Additionally, the responder rate (>= 50% improvement from baseline) was 49% in the NBI-98854 ITT group compared to 18% in placebo (p=0.002). In the per-protocol (PP) group AIMS scores were reduced by 3.3 points for those subjects taking NBI-98854 (p<0.001), with a corresponding responder rate of 59% (p<0.001).

October 7, 2013

Neurocrine Biosciences reported results of a phase IIb study of NBI-98854 for the treatment of tardive dyskinesia. At week two, the randomized study included 109 subjects, including 54 placebo subjects and 27 and 26 subjects who were randomized to the 50mg and 100mg of NBI-98854, respectively. The average age of participants was 55 years and males made up approximately two-thirds of the subjects. All subjects were on stable doses of antipsychotic medication. The 50mg dose of NBI-98854 did not meet the primary endpoint in the phase IIb study, while the 100mg dose showed a statistical and clinically significant improvement. AIMS scores were reduced by 5.5 points in the 100mg per-protocol (PP) group compared to a reduction of 2.7 points in placebo (p=0.008), and the responder rate (>= 50% improvement from baseline) was 48% in the 100mg group compared to 23% in placebo (p=0.034). The 100mg dose was expected to be a maximum tolerated dose based on earlier data; however, in this patient population 100mg was well-tolerated.

April 11, 2011

Neurocrine Biosciences reported interim results from a phase IIa trial of NBI-98854 for Tardive Dyskinesia. This Canadian-based, open label, dose escalation trial plans to enroll up to ten subjects with schizophrenia and moderate to severe Tardive Dyskinesia. Data are from six subjects in the initial cohort. The subjects received three, four-day periods of NBI-98854 at increasing doses of 12.5mg, 25mg and 50mg administered once daily. After discontinuation of NBI-98854, a seven-day washout period was followed by a final assessment. The impact of NBI-98854 on the dyskinesia was assessed utilizing the Abnormal Involuntary Movement Scale (AIMS). In this initial cohort of six subjects, the mean baseline score was 14.3. After the twelve days of dosing, the mean AIMS score decreased to 8.4, a reduction of 41.3%. Reduction in abnormal involuntary movements was shown across multiple assessment points. After the seven-day washout period most of the AIMS scores returned to baseline levels.