Objective: To present somnolence-related events over time from 2 studies of once-daily valbenazine, which is approved for chorea in adults with Huntington’s disease: KINECT®-HD (K-HD, NCT04102579), a double-blind, placebo-controlled, Phase 3 trial; and KINECT®-HD2 (K-HD2, NCT04400331), an ongoing open-label study.

Background: In K-HD, somnolence was the most commonly reported treatment-emergent adverse event (TEAE) for valbenazine (15.6% vs 3.2% for placebo).

Method: Participants received once-daily valbenazine (starting dose: 40 mg; target maintenance dose: 80 mg) for 12 weeks (K-HD) or ≤156 weeks with an optional 2-year extension (K-HD2). Both studies included an 8‑week dose-adjustment period followed by maintenance treatment. TEAEs were monitored throughout both studies and data for ≤52 weeks of follow-up are presented for the ongoing K‑HD2 study. Somnolence-related TEAEs included somnolence, fatigue, hypersomnia, lethargy, and sedation. Analyses were based on the date of onset for each somnolence-related TEAE.

Results: The analysis included 64 participants from K-HD and 125 participants from K-HD2 who received valbenazine. In K-HD, 20 (31%) participants experienced ≥1 somnolence-related event, with a total of 23 events. In K-HD2, 59 (47%) participants experienced ≥1 event, with a total of 78 events. All somnolence-related events were mild (K-HD: 78% [18/23]; K-HD2: 74% [58/78]) or moderate (K-HD: 22% [5/23]; K-HD2: 26% [20/78]). Based on the date of onset, somnolence-related events occurred early in valbenazine treatment. In K‑HD and K-HD2, respectively, 39% (9/23) and 31% (24/78) of events occurred during the first 2 weeks of treatment. In contrast, 9% (2/23) of events occurred during Weeks 8-12 of K-HD and 9% (7/78) occurred during Weeks 27-52 of K-HD2. Somnolence-related events led to dose reduction in 11% (7/64) of K-HD participants receiving valbenazine and in 21% (26/125) of K-HD2 participants. Discontinuation due to somnolence-related events occurred in 2% (1/64) and 6% (7/125) of K-HD and K-HD2 participants, respectively.

Conclusion: Somnolence-related events occurred early in K-HD and K-HD2, following initiation of valbenazine treatment. These events were generally mild and the majority of participants experiencing somnolence continued treatment with valbenazine, some with dose reductions. More research will help elucidate characteristics of somnolence in these studies.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/somnolence-related-events-over-time-with-valbenazine-treatment-for-chorea-associated-with-huntingtons-disease/