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The VMAT2 inhibitor showed improvements through 48 weeks, though after halting therapy, some loss of improvement was observed.
Eiry Roberts, MD
New data on valbenazine (Ingrezza, Neurocrine Biosciences) revealed sustained improvements were seen in adults with tardive dyskinesia through 48 weeks, though some loss of improvement was observed upon halting the therapy, suggesting that ongoing treatment may be required.
The results of the assessment of the highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor were presented at the International Association of Parkinsonism and Related Disorders (IAPRD), in Lyon, France.
Using the mean change from baseline in the Abnormal Involuntary Movement Scale (AIMS) total score for assessment, the changes for patients on valbenazine 40 mg (n = 33) and 80 mg (n = 105) were -4.5 and -3.5, respectively, after 8 weeks. At Week 52, those changes were -1.8 and -3.3, for the 40-mg (n = 20) and 80-mg (n = 74) groups, respectively.
“In addition, improvements in TD were noted in global patient and clinician-reported outcomes, with more than 85% of participants in each [valbenazine] dose group having Clinical Global Impression of Change-TD (CGI-TD) and Patient Global Impression of Change (PGIC) scores indicating ‘much improved’ or ‘very much improved’ at 48 weeks of treatment,” Eiry W. Roberts, MD, the chief medical officer of Neurocrine Biosciences, told NeurologyLive.
The KINECT 4 trial examined 40-mg and 80-mg doses of valbenazine in 163 patients. All patients received a 40-mg dose for the first 4 weeks, followed by possible escalation to 80 mg if the CGI-TD score of ≥3 was observed, or the acceptable safety or tolerability at 40 mg was met, based on physician judgement. Those unable to tolerate the higher dose were allowed a reduction back to 40 mg, and those unable to tolerate the lower dose were discontinued.
At Week 52, after a 4-week washout period, upward of 60% of the total participants continued to self-report substantial global improvements. Of those in the 40-mg group, 65% reported PGIC improvements, while 62.2% of those in the 80-mg group reported the same. PGIC scores indicated no change or worsening in 2 patients at Week 48. Comparatively, at Week 52, 16 patients reported no change (n = 3) or worsening (n = 13).
“Tardive dyskinesia is a condition that is often misunderstood and underdiagnosed. By continuing to add to the clinical profile of [valbenazine], we believe these data bring additional insight for physicians and their tardive dyskinesia patients, further demonstrating the effectiveness and tolerability of [valbenazine] for the treatment of tardive dyskinesia over the long term,” Roberts said.
Prior to week 48, the most common reason for discontinuation were adverse events (15.6%), consent withdrawal (7.2%), and loss of follow-up (6.6%). After Week 4 through Week 48, 64.7% of participants experienced ≥1 treatment-emergent adverse events, with a rate of 62.9% in the 40-mg group and 61.7% in the 80-mg group. The most common adverse events across both groups were urinary tract infection (8.5%), headache (5.2%), nasopharyngitis (4.6%), and suicidal ideation (4.6%).
“Prior to the FDA approval of [valbenazine] in 2017, there were no approved treatments for tardive dyskinesia, a condition that is often underdiagnosed and has a significant impact on a patient population already burdened by serious psychiatric disorders,” Roberts said. “These data demonstrate the long-term efficacy and safety of [valbenazine] and the value this treatment brings to patients suffering from this serious, and often isolating, movement disorder.”
“Consistent with previous trials, [valbenazine] was generally well tolerated and no new safety signals were identified,” she added.
In an open-label, rollover study of participants from KINECT 3 (n = 71) or KINECT 4 (n = 90), also presented at IAPRD, 161 patients enrolled, highlighting an overall perception of benefit among trial participants. At baseline, 100% of those on the 40-mg dose (n = 35) and 99.1% of those on the 80-mg dose (n = 117) were expressed some level of satisfaction with the therapy. At Week 48, those rates were 100% and 97.4%, respectively.
At study termination, 138 patients (85.7%) were still receiving treatment. No patients reached Week 72 of the study, as valbenazine became commercially available prior to Week 60 (a point only 4 patients reached). The mean duration of exposure was 19.4 months (range, 9.9 to 26.7).
In terms of adverse events, 98.1% (n = 153) of those with no Columbia- Suicide Severity Rating Scale (C-SSRS) measured suicidal ideation remained without ideation throughout the trial duration. At least 1 treatment-emergent adverse event occurred in 49% of patients, though none occurred at a rate of ≥5%.
1. Singer C, Comella C, Lindenmayer JP, et al. Effects of Long-Term Valbenazine on Tardive Dyskinesia and Patient-Reported Outcomes: Results from the KINECT 4 Study. Presented at IAPRD: Lyon, France; August 19-22, 2018. Accessed August 23, 2018.
2. Lindenmayer JP, Verghese C, Marder SR, et al. Global Improvement and Patient Satisfaction: Results from a Long-Term, Open-Label, Rollover Study of Valbenazine in Tardive Dyskinesia. Presented at IAPRD: Lyon, France; August 19-22, 2018. Accessed August 23, 2018.