SAFETY RESULTS FROM 3 LONG-TERM VALBENAZINE STUDIES IN YOUNGER AND OLDER ADULTS WITH TARDIVE DYSKINESIA.

Introduction Older age is a significant risk factor for developing tardive dyskinesia (TD). Valbenazine, a novel and highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor, is approved to treat TD in adults, regardless of age. We report a comparison of the long-term safety and tolerability of once-daily valbenazine in adults with TD aged ≥55 vs. <55 years. Methods Data were pooled from two phase 3 studies, KINECT 3 (NCT02274558: valbenazine 40 or 80 mg, 6-week double-blind placebo-controlled period, 42-week double-blind extension) and KINECT 4 (NCT02405091: valbenazine 40 or 80 mg, 48-week open-label treatment). KINECT 3/4 study completers could enroll in a subsequent rollover study (NCT02736955: valbenazine 40 or 80 mg, additional ≤72-week open-label treatment or until valbenazine became commercially available). For safety analyses, participants were categorized by age (older, ≥55y; younger, <55y), and valbenazine doses were pooled. Outcomes included treatment-emergent adverse events (TEAEs), vital signs, electrocardiograms (ECGs), and the Columbia-Suicide Severity Rating Scale (C-SSRS). Significance testing between age subgroups (≥55y vs. <55y) was conducted for summary TEAEs. Results Analyses included 383 KINECT 3/4 participants (≥55y=239; <55y=144) and 160 rollover participants (≥55y=109; <55y=51). Mean ages [and ranges] were as follows (older, younger): KINECT 3/4 participants (62.5 [55 to 83] years; 46.9 [26 to 54] years); rollover participants (62.5 [55 to 83] years, 47.9 [34 to 54] years). In KINECT 3/4, the summary of TEAEs in older and younger participants was as follows (≥55y vs. <55y): any TEAE (77.8% vs. 64.6%; P <0.01); serious TEAE (19.2% vs. 10.4%; P <0.05); and discontinuation due to TEAE (19.7% vs. 11.8%; P <0.05). Headache was the most common TEAE in both age subgroups during KINECT 3/4 (≥55y, 9.6%; <55y, 8.3%). In the rollover study, the incidence of TEAEs was not significantly different between older and younger participants (≥55y vs. <55y): any TEAE (53.2% vs. 52.9%; P >0.05); serious TEAE (10.1% vs. 9.8%; P >0.05); and discontinuation due to TEAE (3.7% vs. 9.8%; P >0.05). The most common TEAE was somnolence among older participants (4.6%) and cough among younger participants (9.8%). During both KINECT 3/4 and the rollover study, no clinically important changes in vital signs or ECGs were found in either age subgroup, and most participants (>90%) had no worsening in C-SSRS scores from baseline. Conclusions In older (≥55y) and younger (<55y) adults who received >1 year of once-daily valbenazine for TD, TEAEs and other safety outcomes were consistent with previous long-term analyses. These results confirm that valbenazine is generally safe and well-tolerated in all adults with TD. This research was funded by This research was fully funded by Neurocrine Biosciences, Inc. [ABSTRACT FROM AUTHOR]