Neurocrine begins tourette syndrome clinical trial of NBI-98854

The T-Force study is an open-label, multi-dose, two-week study of 36 subjects with Tourette syndrome. Children and adolescents will receive once-daily dosing of NBI-98854 during a two-week treatment period to assess both the safety and tolerability of NBI-98854 in Tourette patients. Additionally, the Yale Global Tic Severity Scale and the Premonitory Urge for Tics Scale will be employed during the study to assess the impact of NBI-98854 on the patients’ Tourette symptoms. Data readout from this study is expected in 2015.

"Advancing NBI-98854 into clinical evaluation of Tourette syndrome represents another significant achievement for our VMAT2 franchise," said Kevin C. Gorman, President and Chief Executive Officer of Neurocrine Biosciences. "An important aspect of this initial Tourette syndrome trial is that we are exploring NBI-98854 in children age six to eleven, the target age range for therapy."

The T-Force study is an open-label, multiple ascending dose, pharmacokinetic and pharmacodynamic, study to evaluate the safety, tolerability and exposure-response of NBI-98854 in children and adolescents with Tourette syndrome. A total of 36 patients will be evaluated over 14 days of once-daily dosing followed by 7 days off-drug at approximately 10 study centers in the United States.

The study will be divided into two dosing groups consisting of children (ages 6-11) and adolescents (ages 12-18), and each age group will be further divided into three dosing cohorts of six patients each. After completing the initial two weeks of dosing with the first adolescent cohort, an independent review of both safety and pharmacokinetic results will occur prior to escalating the dose level for the second cohort of adolescents.

In parallel, while initiating the second cohort of adolescents, the first cohort of children (ages 6-11) will also be administered NBI-98854 for a two-week period. Subsequent dose escalations for children and adolescents will be based, in part, on the pharmacokinetic and safety data from the previous cohort in each age group.

Additionally, the patient’s Tourette symptoms will be evaluated weekly via the Yale Global Tic Severity Scale, the Premonitory Urge for Tics Scale as well as an overall Clinical Global Impression in Tourette syndrome Scale.

Tourette syndrome is a neurological disorder that consists of rapid, non-rhythmic stereotyped motor and vocal tics. Motor tics are typically characterized by facial grimacing, head jerks, extremity movements and other dystonic movements. Vocal tics typically include grunting, throat clearing, and repeating words and phrases.

The average age of onset for Tourette syndrome is at six years, with symptoms reaching their peak severity at approximately age ten. Tourette syndrome is more commonly diagnosed in males than females and may be associated with attention deficit hyperactivity disorder and obsessive compulsive disorder. There are approximately 400,000 people with Tourette syndrome in the United States.

VMAT2 is a protein concentrated in the human brain that is primarily responsible for re-packaging and transporting monoamines (dopamine, norepinephrine, serotonin, and histamine) in pre-synaptic neurons. NBI-98854, developed in the Neurocrine laboratories, is a novel, highly-selective VMAT2 inhibitor that modulates dopamine release during nerve communication, while at the same time having minimal impact on the other monoamines, thereby reducing the likelihood of "off-target" side effects. NBI-98854 is designed to provide low, sustained, plasma and brain concentrations of active drug to minimize side effects associated with excessive monoamine depletion.

Modulation of neuronal dopamine levels in diseases such as tardive dyskinesia, Tourette syndrome, Huntington’s chorea, schizophrenia, and tardive dystonia, which are characterized, in part, by a hyperdopaminergic state, should provide symptomatic benefits for patients with these diseases.

In addition to this Tourette syndrome study, the Company will initiate the Phase III pivotal study assessing NBI-98854 in tardive dyskinesia during the fourth quarter of 2014.

The Company has two distinct Investigational New Drug Applications, tardive dyskinesia and Tourette syndrome, open with the Division of Psychiatry Products at the FDA.