New Post-Hoc Analysis: Ingrezza 40 mg Leads to Clinically Meaningful Improvements in Tardive Dyskinesia Symptoms

Neurocrine Biosciences today announced the presentation of a new post-hoc analysis from the phase 3, open-label KINECT 4 study, which demonstrates that patients treated continuously for 48 weeks with the 40 mg dose of once-daily valbenazine (Ingrezza) capsules experienced clinically meaningful improvements in tardive dyskinesia (TD) symptoms.¹

Ingrezza is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved by the US Food and Drug Administration for the treatment of adults with tardive dyskinesia and the treatment of chorea associated with Huntington disease.² Ingrezza offers a therapeutic dose from day 1 with no required titration.

"The KINECT 4 post-hoc analysis demonstrated the rapid, sustained, long-term clinical benefit of treatment with Ingrezza at the lowest available dose of 40 mg," said Sanjay Keswani, MD, the chief medical officer of Neurocrine Biosciences. "Ingrezza is the only VMAT2 inhibitor that allows patients to start at a therapeutic dose, stay at that dose or adjust to 60 mg or 80 mg, based on individual response and tolerability. These findings add to previously published data supporting 40 mg as an effective, long-term treatment option."

The KINECT 4 phase 3, open-label study evaluated the long-term efficacy, safety, and tolerability of Ingrezza in adults with TD. Participants in the post-hoc analysis received Ingrezza 40 mg once daily for the first 4 weeks, with the option to escalate to 80 mg daily at week 4, based on tolerability and clinical response. From week 4 through week 48, dose reduction from 80 mg to 40 mg was permitted based on individual tolerability.

The analysis included participants in the Ingrezza 40 mg group (n=45), who received 40 mg throughout the entire study, as well as participants in the Ingrezza 80/40 mg group (n=11), who increased to 80 mg at week 4 and subsequently reduced to 40 mg. Efficacy was evaluated at all postbaseline visits through end of treatment (week 48) using clinician- and patient-reported changes in TD severity, as measured by the Abnormal Involuntary Movement Scale (AIMS), Clinical Global Impression of Change-TD (CGI-TD) and Patient Global Impression of Change (PGIC).

Efficacy outcomes demonstrated several clinically meaningful improvements in TD that were sustained throughout the 48-week treatment period in both the Ingrezza 40 mg and Ingrezza 80/40 mg groups. At all postbaseline visits from week 4 to week 48, the mean change from baseline in AIMS total score exceeded the minimally clinical important difference threshold, demonstrating rapid and continuous improvements with Ingrezza treatment. In participants who received 40 mg throughout the entire study, the percentage meeting the AIMS response threshold (≥50% total score improvement from baseline) generally increased over time, with 90% (18/20) of those completing 48 weeks reaching this threshold. The analysis also showed that participants who reduced their dose from 80 mg to 40 mg for tolerability reasons achieved similar therapeutic benefits.

Additionally, from week 8 through week 48, more than half of all participants across both treatment groups met the response threshold for CGI-TD and PGIC, with 90% (18/20) of participants on continuous Ingrezza 40 mg treatment being "much improved" or "very much improved" at week 48 per clinician assessment (CGI-TD) and patient self-report (PGIC).

Notably, efficacy outcomes with Ingrezza 40 mg were comparable with those achieved with 80 mg in the original KINECT 4 study, and the safety and tolerability of treatment was consistent with the known profile of Ingrezza with no new concerns identified. Most treatment-emergent adverse events were mild or moderate in intensity. The most common adverse effects in individuals with TD are sleepiness and tiredness.

Investigators will present findings at the American Psychiatric Nurses Association 39th Annual Conference, taking place October 15-18 in New Orleans.

References

1. Neurocrine Biosciences presents new KINECT® 4 post-hoc analysis demonstrating rapid and sustained therapeutic efficacy of INGREZZA® (valbenazine) 40 mg capsules. News release. October 17, 2025. Accessed October 17, 2025. https://www.prnewswire.com/news-releases/neurocrine-biosciences-presents-new-kinect-4-post-hoc-analysis-demonstrating-rapid-and-sustained-therapeutic-efficacy-of-ingrezza-valbenazine-40-mg-capsules-302586928.html

2. 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