NBI-98854 - Vesicular Monoamine Transporter 2 Inhibitor (VMAT2)To address the unmet medical needs of patient suffering from TD, Neurocrine is developing NBI-98854. NBI-98854 is a potent, highly selective, VMAT2 inhibitor that is effective in regulating the levels of dopamine release during nerve communication, while at the same time having minimal impact on the other monoamines. This selectivity may reduce the likelihood of “off target” side effects. Additionally, we have designed this novel compound to provide low, sustained, plasma and brain concentrations of the active drug to minimize the potential side effects associated with excessive dopamine depletion. With these features, NBI-98854 is anticipated to be well tolerated in patients.
The next step in our VMAT2 development program is to complete a multiple, repeated dose Phase I study in healthy male volunteers. Assuming successful completion of the study, we intend to approach the FDA regarding the filing of an Investigational New Drug application in the United States with the express purpose of initiating a proof-of-concept study in patients with tardive dyskinesia late in 2010. We believe that the potential efficacy and safety profile of NBI-98854 will address many of the shortcomings of current off-label treatments. With an additional development plan in Tardive Dyskinesia, NBI-98854 may well be useful in other disorders, such as Huntington’s chorea, schizophrenia, Tourette’s syndrome, and tardive dystonia. |
During 2009, our VMAT2 inhibitor completed a Phase I single ascending dose clinical trial in healthy male volunteers in Canada under an approved Clinical Trial Application with Health Canada. This trial showed our VMAT2 inhibitor to be generally safe and well tolerated. There were no serious adverse events, clinically significant drug-related laboratory abnormalities or clinically significant ECG findings. The characteristics of our VMAT2 inhibitor met the pre-specified pharmacokinetic requirements for the trial: dose proportionality, low maximum concentration with adequate area-under-curve for drug exposure, low variability, and a half-life which supports once per day dosing.