NBI-98854, an experimental drug for tardive dyskinesia being developed by Neurocrine Biosciences, led to a statistically significant reduction in symptoms of the movement disorder in a phase 3, placebo-controlled trial called Kinect 3, the company announced Thursday.
NBI-98854 is a novel, highly selective inhibitor of the vesicular monoamine transporter 2 (VMAT2) protein that modulates neuronal dopamine levels. It is designed to provide “low, sustained, plasma and brain concentrations of active drug to minimize side effects associated with excessive monoamine depletion,” the company notes in a news release.
“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,” they say.
The US Food and Drug Administration (FDA) granted NBI-98854 Breakthrough Therapy Designation for the treatment of tardive dyskinesia in October 2014.
The Kinect 3 study involved 234 patients with moderate to severe tardive dyskinesia with underlying schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder. Patients were randomly allocated to receive either placebo or NBI-98854 once daily at a dose of 40 mg or 80 mg for 6 weeks. From weeks 6 through 48, during the open-label portion of the trial, all patients were taking NBI-98854 (40 or 80 mg once daily).
According to the company, there was a significant difference favoring NBI-98854 in the prespecified primary efficacy end point ― change from baseline in the Abnormal Involuntary Movement Scale (AIMS) at week 6 in the 80-mg, once-daily dosing group compared with the placebo group.
The AIMS ratings at week 6 for the 80-mg, once-daily NBI-98854 intention-to-treat population was reduced 3.1 points more than for the patients receiving placebo (P < .0001).
NBI-98854 was generally well tolerated during the 6-week, placebo-controlled treatment period. The frequency of adverse events was similar among all treatment groups, and treatment-emergent adverse effects were consistent with those of prior studies, the company says.
At baseline, patients had “minimal symptoms” on the Barnes Akathisia Ratings Scale for akathisia and the Simpson-Angus Scale for parkinsonism, and there was no worsening during 6 weeks of treatment.
No drug-drug interactions were identified in study patients, who were taking a wide range of psychotropic and other concomitant medications.
“We are very pleased with the outstanding efficacy and side effect profile demonstrated by NBI-98854 in the Kinect 3 study. The efficacy data from this pivotal phase 3 study completes our placebo-controlled dataset for NBI-98854 in tardive dyskinesia,” Kevin C. Gorman, PhD, Neurocrine president and chief executive officer, said in the release.
“We will now turn our focus to completing the open-label safety portion of the studies in tardive dyskinesia patients and compiling the data for both doses of NBI-98854 to be included in the New Drug Application we intend to file with the FDA in 2016,” he said.