Effects of Long-Term Valbenazine on Tardive Dyskinesia and Patient-Reported Outcomes: Results from the KINECT 4 Study (P4.078)

Objective: To explore the long-term effects of once-daily valbenazine on tardive dyskinesia (TD). Background: Valbenazine (INGREZZA®) was approved for TD based on several short-term placebo-controlled trials, a blinded extension study, and the long-term KINECT 4 (NCT02405091) study, presented here. Design/Methods: Adults with TD (including de novo patients and participants from prior valbenazine studies) received 48 weeks of open-label treatment with valbenazine. Dosing was initiated at 40 mg, with escalation to 80 mg at Wk4 based on efficacy (inadequate/insufficient clinical response per investigator judgment) and tolerability. Dose reduction back to 40 mg was allowed in participants who could not tolerate the 80 mg dose. Change from baseline (CFB) in the Abnormal Involuntary Movement Scale (AIMS) total score was used to assess changes in TD. Additional efficacy assessments included the Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change-TD (CGI-TD) scales. Standard safety methods were applied, including treatment-emergent adverse event (TEAE) reporting. Results: In the safety population (N=163), 107 participants received/tolerated the 80 mg dose, 45 did not require escalation from the 40 mg dose, and 11 were escalated to 80 mg but later required reduction to 40 mg. Mean CFB to Wk48 in AIMS total score indicated TD improvements in all dose groups: 80 mg, −11.0; 40 mg, −10.2; 80/40 mg, −7.2. At Wk48, >75% of participants in each dose group had a PGIC score ≤2 (much improved or very much improved): 80 mg, 89.2%; 40 mg, 90.0%; 80/40 mg, 77.8%. Mean CGI-TD scores at Wk48 (80 mg, 1.6; 40 mg, 1.7; 80/40 mg, 2.3) indicated clinically meaningful long-term improvement for all dose groups. Less than 15% of all participants had a serious TEAE (12.9%) or TEAE leading to discontinuation (14.7%). Conclusions: Consistent with previous trials, substantial clinician- and patient-reported improvements were observed in adults with TD receiving once-daily valbenazine for 48 weeks. Valbenazine was generally well tolerated and no safety signals were detected. Study Supported by: Neurocrine Biosciences, Inc. Disclosure: Dr Factor has nothing to disclose. Dr. Kane has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alkermes, Allergan, Bristol-Myers Squibb, Intra Cellular Therapies, Janssen, Lundbeck, Minerva, Neurocrine, Otsuka, Pierre Fabre, Reviva, Sunovion, Takeda and Teva. Dr. Kane has received compensation for serving on the Board of Directors of LB Pharma, MedAvante and The Vanguard Research Group. Dr. Marder has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory panels or consulted for Allergan, Boeringer-Ingelheim, Gedeon Richter, Lundbeck, Neurocrine Biosciences, Otsuka, Roche, Takeda, and Teva. Dr. Marder has received research support from Research support from Forum and Neurocrine Biosciences. Dr. Hauser has nothing to disclose. Dr. Farahmand has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Neurocrine Biosciences, Inc. Dr. Jimenez has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Neurocrine Biosciences, Inc. Dr. Burke has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Neurocrine Biosciences, Inc. Dr. Siegert has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Neurocrine Biosciences, Inc. Dr. Liang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Neurocrine Biosciences, Inc.