US-based biotechnology firm Neurocrine Biosciences’ Ingrezza (valbenazine) has failed to meet the primary endpoint in its Phase II T-Force GREEN clinical trial to treat Tourette syndrome.
Ingrezza is a small molecule inhibitor of VMAT2 and is believed to regulate nerve signalling by decreasing the dopamine levels released in the brain.
The pre-specified primary endpoint of the randomised, double-blind, placebo-controlled, multi-dose, parallel group trial was the change from baseline between the placebo and active groups as measured in the Yale global tic severity scale (YGTSS) at week six.
The analysis of exposure-response revealed that the doses used in the trial were below the therapeutic range required for adequate tic reduction.
The Phase II trial evaluated the safety, tolerability and efficacy of two different doses in 98 children and adolescents over six weeks.
Neurocrine chief medical officer Christopher O'Brien said: "This study showed that we underestimated the Ingrezza dose needed for the pediatric population but also provided us with a clear-cut view into the level of dosing required for future studies.
"We have developed a complete exposure-response model from this study, that we believe accurately defines the appropriate dose-range, to be tested in the next clinical study that will be started later this year.”
During the treatment period, the subset of subjects with pharmaceutical exposure in the appropriate range showed a substantial decrease in tics, while patients with sub-therapeutic exposure demonstrated a tic reduction comparable to placebo.
The adverse events observed during the trial were found to be consistent with the previous trials.
Ingrezza is also being studied in another fixed-dose, open-label Phase II trial to evaluate its long-term safety and tolerability in approximately 90 children and adolescents and 90 adults, who completed either the T-Force GREEN or T-Forward trial.