Neurocrine presents Ingrezza efficacy, safety data for tardive dyskinesia

At the American Academy of Neurology annual meeting, researchers presented long-term efficacy and safety data supporting the recent FDA approval of Ingrezza for tardive dyskinesia in adults.

“We are very pleased to present additional robust data from the largest ever clinical program in tardive dyskinesia at this year’s American Academy of Neurology Annual Meeting,” Chris O'Brien, MD, FAAN, chief medical officer at Neurocrine, said in a press release. “Over 1,000 persons have participated in more than 20 Ingrezza clinical trials, with consistent and strong results demonstrated by the first and only FDA-approved treatment for adults with tardive dyskinesia. These expanded safety, efficacy and pharmacologic findings continue to illustrate Ingrezza’s differentiated potential and what it offers to an underserved community.”

To determine efficacy of Ingrezza (valbenazine, Neurocrine Biosciences) for tardive dyskinesia, researchers conducted a phase 3 trial that included a 6-week, double-blind, placebo-controlled period, a 42-week valbenazine extension period, and a 4-week treatment-free follow-up. Adults with tardive dyskinesia and schizophrenia, schizoaffective disorder or mood disorder initially randomized to receive placebo were re-randomized to 80 mg or 40 mg of valbenazine per day, while those initially randomized to valbenazine continued with the same doses.

At week 48, mean change in Abnormal Involuntary Movement scale (AIMS) scores were –4.8 for participants who received 80 mg of valbenazine and –3 for those who received 40 mg.

Fifty-two percent of the 80-mg group and 28% of the 40-mg group exhibited response to valbenazine, indicated by at least a 50% reduction in AIMS scores.

From week 48 to 52, AIMS scores increased from 6.2 to 9.8 among participants who received 80 mg of valbenazine and from 6.8 to 8.4 among those who received 40 mg of valbenazine, indicating worsening of tardive dyskinesia during the nontreatment period.

At week 48, mean improvements in Clinical Global Impression of Change scores were 2.1 among participants who received 80 mg of valbenazine and 2.4 among those who received 40 mg of valbenazine.

The majority of participants who received 80 mg (76%) or 40 mg (59%) of valbenazine had “much improved” or “very much improved” Clinical Global Impression of Change scores.

Safety, tolerability

To assess safety and tolerability of valbenazine for tardive dyskinesia, researchers pooled long-term exposure data from KINECT (n = 46), KINECT 3 (n = 220) and KINECT 4 (n = 161). Mean duration of valbenazine treatment was 6 months and 85.5% of participants were taking concomitant antipsychotic medications.

The most common treatment-emergent adverse events were somnolence (4.7%), fatigue (3.7%) and dry mouth (2.3%).

Serious treatment-emergent adverse events occurred among 12.6% of participants and led to dose reduction in 6.1% and discontinuation in 13.6%.

Researchers did not observe worsening of psychiatric symptoms of clinically significant drug-induced extrapyramidal symptoms.

“Tardive dyskinesia improved in subjects receiving valbenazine for 48 weeks, with tardive dyskinesia reappearing after medication was withdrawn. Together with the long-term safety profile, these results indicate that long-term valbenazine may be beneficial for managing tardive dyskinesia,” the researchers concluded. – by Amanda Oldt

Reference:

Factor S, et al. Efficacy of valbenazine (NBI-98854) in subjects with tardive dyskinesia: Results of a long-term study (KINECT 3 extension). Presented at: American Academy of Neurology Annual Meeting; April 22-28, 2017; Boston.

Remington G, et al. Safety and tolerability of valbenazine (NBI-98854) in subjects with tardive dyskinesia: Results of long-term exposure data from three studies. Presented at: American Academy of Neurology Annual Meeting; April 22-28, 2017; Boston.

Disclosure: The study was supported by Neurocrine Biosciences, Inc.