Long-term data shows efficacy, safety of valbenazine for tardive dyskinesia

SAN DIEGO — Data showing long-term efficacy and pharmacokinetic profile of Ingrezza capsules, recently approved by the FDA for treatment of tardive dyskinesia, was presented at the American Psychiatric Association Annual Meeting.

“This year’s annual meeting of the APA is an excellent opportunity to present additional data and analyses from the extensive clinical development program both supporting and differentiating Ingrezza,” Chris O’Brien, MD, chief medical officer of Neurocrine, said in a press release. “We are particularly pleased to share this information with psychiatrists who now have access to the first and only FDA approved treatment for tardive dyskinesia patients.”

To assess efficacy of Ingrezza (valbenazine, Neurocrine Biosciences) for tardive dyskinesia in mood and schizoaffective disorders, researchers conducted the KINECT 3 study, which included a 6-week, double-blind, placebo-controlled period (n = 205), a 42-week valbenazine extension period (n = 124) and a 4-week washout period (n = 121). Study participants were randomly assigned to received 80 mg or 40 mg of valbenazine or placebo. Participants who completed the double-blind placebo-controlled period were re-randomized from placebo to valbenazine or continued valbenazine treatment at the same dose.

Mood disorders

Participants with mood disorders accounted for 77 participants in the double-blind placebo-controlled period and 73 in the valbenazine extension period.

At week 6, participants with mood disorders exhibited a mean Abnormal Involuntary Movement (AIMS) score improvement of –3.6 for those who received 80 mg of valbenazine; 2.4 for those who received 40 mg; and –0.7 for placebo.

At week 48, mean AIMS score changes continued to favor valbenazine, with mean changes of –5.8 and –4.2 among participants who received 80 mg or 40 mg, respectively.

By week 52, AIMS mean scores were trending towards baseline levels among both dose groups, indicating a reemergence of tardive dyskinesia.

Clinical Global Impression of Change (CGI-TD) scores followed similar patterns in weeks 6, 48 and 52.

AIMS responder rates were greater among participants who received valbenazine at week 6 (38.5% for 80 mg; 19% for 40 mg; 7.7% for placebo), increased at week 48 (56% for 80 mg; 33.3% for 40 mg), and decreased at week 52 (16.7% for 80 mg; 27.8% for 40 mg).

CBI-TD responder rates exhibited a similar pattern.

Schizophrenia and schizoaffective disorders

Participants with schizophrenia or schizoaffective disorders accounted for 148 participants in the double-blind placebo-controlled period and 125 in the valbenazine extension period.

At week 6, AIMS mean score improvements were greater among participants who received valbenazine, with a change of –2.9 for those who received 80 mg; –1.6 for 40 mg; and 0.3 for placebo.

At week 48, AIMS score changes indicated continued improvement in tardive dyskinesia, with mean changes of –4.2 for participants who received 80 mg and –2.5 for 40 mg.

By week 52, AIMS scores were returning to baseline levels, which indicated re-emergence of tardive dyskinesia.

At week 6, CGI-TD mean scores were 3 among the 80-mg group; 2.9 for the 40-mg group; and 3.2 for the placebo group.

At week 48, CGI-TD mean scores were 2.2 among the 80-mg group and 2.4 for the 40-mg group.

At week 52, CGI-TD mean scores were 3.4 among the 80-mg group and 3.3 for the 40-mg group.

AIMS responder rates were greater among participants who received valbenazine at week 6 (40.9% for 80 mg; 26.2% for 40 mg; 9.3 for placebo), increased at week 48 (50% for 80 mg; 26.2% for 40 mg), and decreased at week 52 (21.6% for 80 mg; 9.5% for 40 mg).

CBI-TD responder rates exhibited a similar pattern.

Long-term safety and tolerability

To assess long-term safety and tolerability of valbenazine, researchers analyzed data from KINECT, KINECT 3, and KINECT 4 among 430 individuals who underwent safety assessments including adverse events laboratory tests, vital signs, electrocardiograms, and extrapyramidal symptom scales.

Overall, 71.7% of participants had schizophrenia or schizoaffective disorder, 28.3% had a mood disorders and 85.5% were taking an antipsychotic.

Treatment-emergent adverse events were reported by 66.5% of the cohort; serious adverse events were reported by 14.2%; and discontinuations due to adverse events were reported by 14.7%.

Treatment-emergent adverse events were more common in participants with mood disorders (71.9% vs. 64.4%).

Among participants with schizophrenia, the most common treatment-emergent adverse events were urinary tract infections (6.1%), headache (5.8%) and somnolence (5.2%).

Among participants with mood disorders, the most common treatment-emergent adverse events were headache (12.4%), urinary tract infection (10.7%) and somnolence (9.1%).

Mean score changes from baseline to treatment end indicated participants with mood disorders or schizophrenia or schizoaffective disorders maintained psychiatric stability.

Scores remained “relatively stable” during 4-week drug-free follow-up periods and mean changes in laboratory measures, vital signs, electrocardiogram results and extrapyramidal symptom scales were minimal. – by Amanda Oldt

Reference:

Correll CU, et al. Efficacy of valbenazine (NBI-98854) in treating subjects with tardive dyskinesia and mood disorder.

Josiassen RC, et al. Long-term safety and tolerability of valbenazine (NHI-98854) in subjects with tardive dyskinesia and a diagnosis of schizophrenia or mood disorder.

Kane JM, et al. Efficacy of valbenazine (NBI-98854) in treating subjects with tardive dyskinesia and schizophrenia or schizoaffective disorder.

Presented at: American Psychiatric Association Annual Meeting; May 20-24, 2017; San Diego.

Disclosure: Correll reports financial ties with Alkermes, Forum Pharmaceuticals, Janssen, Lundbeck, Otsuka Pharmaceuticals, Pfizer, Sunovion Pharmaceuticals Inc., Supernus, Takeda Pharmaceuticals, Teva Pharmaceuticals. Kane reports financial ties with Alkermes, Allergan, Eli Lilly and Company, Forum Pharmaceuticals, Genentech, Intracellular Therapies, Janssen, Johnson & Johnson, Lundbeck, Neurocrine Biosciences, Inc., Otsuka Pharmaceuticals, Pierre Fabre, Reviva, Roche, Sunovion Pharmaceuticals Inc., and |Teva Pharmaceuticals. Josiassen reported no relevant financial disclosures.