Managing Tardive Dyskinesia: New Data from Phase 3 Study of Ingrezza

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New data from a post hoc analysis of Neurocrine Biosciences’ phase 3 KINECT®-4 study of Ingrezza (valbenazine) capsules, which assessed long-term outcomes for the management of tardive dyskinesia (TD), demonstrated that almost all study participants saw clinically meaningful improvements in TD symptom severity by week 48.¹

“TD is a persistent, debilitating disorder requiring continuous treatment to effectively and sustainably improve symptoms over time," said Eiry W. Roberts, MD, chief medical officer at Neurocrine Biosciences. “This post hoc analysis, along with previous long-term analyses, demonstrate the reliable, long-term efficacy and tolerability of one-capsule, once-daily Ingrezza to help inform use of this treatment in clinical practice.”

In the phase 3, open-label KINECT®-4 study, 163 participants with moderate to severe TD and comorbid schizophrenia, schizoaffective disorder, or mood disorder received once-daily Ingrezza for 48 weeks of open-label treatment followed by a 4-week washout. Dosing began at 40 mg/day in all participants, which was then escalated to 80 mg/day at week 4 based on effectiveness and tolerability. Investigators allowed dose reduction back to 40 mg in participants who could not tolerate the 80 mg dose. Participants were discontinued if the new dose was not tolerated.

Investigators conducted on-site assessments of TD severity and found that participants experienced improvements during long-term treatment as demonstrated by mean change from baseline to week 48 in Abnormal Involuntary Movement Scale (AIMS) total score with Ingrezza 40 mg/day (-10.2) or 80 mg/day (-11.0). At week 4, 55% of participants experienced clinically meaningful improvement in TD symptom severity on the 40 mg dose, defined as a reduction of at least 2 points in the AIMS total score used to assess the severity of involuntary movements in different body regions. Approximately 95% of participants reached this threshold as soon as week 24, and 97% achieved it by week 48. Improvement in TD symptoms was sustained throughout treatment, with an AIMS mean total score reduction from baseline to week 48 of 10.5. Furthermore, approximately 86% of participants met the response threshold of at least 50% AIMS improvement, and 52% met the higher threshold of at least 70% AIMS improvement at week 48.

Notably, more than 88% of patients and health care professionals rated participants' symptoms as "much improved" or "very much improved" at week 48, as measured by both the Patient Global Impression of Change and the Clinical Global Impression of Change-TD.

Ingrezza was generally well tolerated, consistent with previous studies. Treatment emergent adverse events that occurred in more than 5% of all participants (combined dose groups) after week 4 were urinary tract infection (8.5%) and headache (5.2%). Investigators indicated that changes from baseline in psychiatric stability, vital signs, electrocardiogram parameters, and laboratory test values were generally small and not clinically significant.

The US Food and Drug Administration (FDA) first approved Ingrezza for the treatment of adults with TD back in April 2017.² Recently in April 2024, the FDA also approved Ingrezza Sprinkle, a new oral granules formulation of the medication, for the treatment of adults with TD.³

Researchers believe valbenazine functions as a highly selective inhibitor of the VMAT2 vesicular monoamine transporter, which results in decreased availability of dopamine in the presynaptic cleft and leads to decreased dopaminergic activation of the striatal motor pathway. When compared with other pharmaceutical agents, valbenazine is found to be more selective and limited in its toxicities.⁴

References

1. Neurocrine Biosciences announces publication of phase 3 KINECT®-4 post hoc analysis demonstrating clinically meaningful and sustained improvement in tardive dyskinesia with long-term use of Ingrezza® (valbenazine) capsules. News release. May 21, 2024. Accessed May 22, 2024. https://neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-announces-publication-phase-3-kinectr-4

2. Terry M. Nothing's gonna stop Neurocrine now: shares jumped on FDA approval of the first and only drug to treat tardive dyskinesia for adults. BioSpace. April 13, 2017. Accessed May 22, 2024. https://www.biospace.com/article/nothing-s-gonna-stop-neurocrine-now-shares-jumped-on-fda-approval-of-the-first-and-only-drug-to-treat-tardive-dyskinesia-for-adults-/

3. Duerr HA. Ingrezza Sprinkle capsules received FDA approval for tardive dyskinesia in adults. Psychiatric Times. April 30, 2024. https://www.psychiatrictimes.com/view/ingrezza-sprinkle-capsules-received-fda-approval-for-tardive-dyskinesia-in-adults

4. Gupta H, Moity AR, Jumonville A, et al. Valbenazine for the treatment of adults with tardive dyskinesia. Health Psychol Res. 2021;9(1):24929.