VMAT2 inhibitor / Neurocrine - LARVOL DELTA

Disparities in Tardive Dyskinesia Diagnosis and Treatment Among the US Medicare Population (ISPOR 2025) - "Among patients diagnosed with TD, a nested analysis was performed evaluating likelihood of appropriate treatment, defined as initiation of an FDA-indicated VMAT2 inhibitor ≤90 days on/after diagnosis... Black and dual-eligible patients were significantly more likely to be diagnosed with TD, and Latino patients significantly less likely. Subsequent likelihood of appropriate TD treatment was lower among LTC patients and higher among dual-eligibles. Improvements in TD screening and treatment education may help reduce TD burden in vulnerable groups."

Clinical • Medicare • Reimbursement • US reimbursement • CNS Disorders • Movement Disorders

Impact of Valbenazine on Improvements in Disability and Functional Impairment in Patients With Tardive Dyskinesia (TD): Sheehan Disability Scale (SDS) Results From a Phase 4 Randomized Withdrawal Study (NCT03891862) (ISPOR 2025) - P4 | "A phase 4 study assessed persistence of effects of valbenazine, a VMAT2 inhibitor approved for TD and chorea associated with Huntington's disease, versus placebo. Patients received open-label (OL) valbenazine up to 80 mg for 8 weeks then were randomized to either continue valbenazine or receive placebo for 8 weeks. Patients receiving 8 weeks OL valbenazine had improvements in functioning and disability, evidenced by reduced SDS scores. Patients randomized to valbenazine experienced continued improvements in all SDS domains, including significant enhancements in social life and family/home life compared to those randomized to placebo."

Clinical • P4 data • Huntington's Disease • Movement Disorders

Impact Of Valbenazine On Improvements In Health-Related Quality of Life (HRQoL) In Patients With Tardive Dyskinesia (TD): EQ-5D-5L Results From A Phase 4 Randomized Withdrawal Study (NCT03891862) (ISPOR 2025) - P4 | "A phase 4 study assessed persistence of effects of valbenazine, a VMAT2 inhibitor approved for treatment of TD and chorea associated with Huntington's disease, versus placebo. Patients received open-label (OL) valbenazine up to 80 mg for 8 weeks, then were randomized to continue valbenazine or receive placebo for 8 weeks. Patients receiving 8 weeks of OL valbenazine had improvements in HRQoL via the EQ-5D-5L. Patients randomized to valbenazine experienced continued improvements in all EQ-5D-5L items including significant improvements in mobility and anxiety/depression compared to patients randomized to placebo."

Clinical • HEOR • P4 data • CNS Disorders • Depression • Huntington's Disease • Mood Disorders • Movement Disorders • Pain • Psychiatry

Indirect Treatment Comparison for Early Efficacy of VMAT2 Inhibitors for Tardive Dyskinesia and Chorea Associated with Huntington's Disease (ISPOR 2025) - "OBJECTIVES: Two vesicular monoamine transporter 2 (VMAT2) inhibitors, valbenazine and deutetrabenazine, are approved for both tardive dyskinesia (TD) and chorea associated with Huntington's disease (HD). Favorable improvements were found with valbenazine versus deutetrabenazine during early treatment for both TD and HD-chorea. Magnitude of effect and time needed to reach an effective dose are important considerations when choosing a medication to treat the hyperkinetic movement disorders of TD or HD-chorea."

Clinical • Huntington's Disease • Movement Disorders

Longitudinal Treatment Patterns of Chorea in North American Patients with Huntington's Disease: Data from Enroll-HD. (PubMed, Neurol Ther) - "Only 36.1% of participants with chorea were taking a medication indicated for chorea, and, while 49.9% of treated participants received VMAT2 inhibitors first-line, approximately half were prescribed off-label alternatives. It is unclear why patients with indications for treatment were untreated or why off-label alternatives were prescribed. Future research should elaborate on these observations."

Journal • CNS Disorders • Huntington's Disease • Movement Disorders

Dissemination of VMAT-2 Inhibitors: A New Class Drug for Tardive Dyskinesia and Huntington Disease. (PubMed, Neurol Clin Pract) - "Our analysis aims to examine the dissemination of 2 vesicular monoamine transporter 2 (VMAT-2) inhibitors, deutetrabenazine and valbenazine, in the market. Nonconsulting services constituted the largest sum of industry payments for both medications. Further research exploring the causative factors of new medication uptake is needed to better understand how medications disseminate across the market."

Journal • Genetic Disorders • Huntington's Disease • Movement Disorders • Psychiatry

The Impact of Diagnosing Provider Type on Longitudinal Care for Patients With Newly Diagnosed Huntington’s Disease (HD) (ISPOR 2024) - "57% received antipsychotic and/or VMAT2 inhibitor treatment within the first-year post-diagnosis. HD patients are most often diagnosed by neurologists or PCPs. Although the same type of provider who diagnosed the patient typically manages their HD follow-up, no differences in HCRU were found between provider types."

Clinical • CNS Disorders • Huntington's Disease • Movement Disorders • Psychiatry

TeleSCOPE 2.0: A Follow-up Real-world Study of Telehealth for the Detection and Treatment of Drug-induced Movement Disorders (DIMD) (AAN 2024) - "Design/T2 was fielded (5/18-6/9/2023) to clinicians affiliated with neurology/psychiatry practices who prescribed VMAT2 inhibitors or benztropine for DIMDs in the past 6 months and saw ≥15% of patients via telehealth at peak and post-COVID.100 neurologists, 100 psychiatrists, and 105 NP/PAs responded. Clinicians see value in telehealth, but it's still not as effective as in-person – requiring 1 additional telehealth visit for DIMD diagnosis; >50% of clinicians recommend patients come in-person to confirm DIMD diagnosis. Significant barriers to telehealth remain."

Clinical • Real-world • Real-world evidence • Infectious Disease • Movement Disorders • Novel Coronavirus Disease • Pain • Psychiatry

Exploring real-world symptom impact and improvement in well-being domains for tardive dyskinesia in VMAT2 inhibitor-treated patients via clinician survey and chart review. (PubMed, Ment Health Clin) - "A web-based survey was offered to physicians, nurse practitioners, and physician assistants based in the US who prescribed valbenazine for TD within the past 24 months...In VMAT2-treated patients with TD symptom improvement, clinicians reported concomitant improvement in psychiatric disorder symptoms and in social and physical well-being. Regular assessment of TD impact on these types of domains should occur simultaneously with movement disorder ratings when evaluating the value of VMAT2 inhibitor therapy."

Journal • Real-world • Real-world evidence • Review • CNS Disorders • Mental Retardation • Movement Disorders • Psychiatry

Global Improvements and Psychiatric Stability in Adults With Tardive Dyskinesia and Mood Disorder: Post Hoc Analyses of Two Long-Term Valbenazine Studies (ISBD 2023) - "Global improvements and psychiatric status were evaluated in patients with TD who received long-term treatment with valbenazine, a highly selective VMAT2 inhibitor approved for TD. Participants with TD and a primary mood disorder who received long-term treatment with once-daily valbenazine met rigorous thresholds for global improvement of TD while maintaining their psychiatric stability."

Clinical • Retrospective data • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Global Improvements and Psychiatric Stability in Adults with Tardive Dyskinesia: Post Hoc Analyses of Two Long-Term Valbenazine Studies (AAN 2023) - "Objective To evaluate global improvements and psychiatric status in patients with tardive dyskinesia (TD) who received long-term treatment with valbenazine, a highly selective VMAT2 inhibitor approved for TD. No emergence of suicidal ideation/behavior was observed. Conclusions Patients with TD who received long-term treatment with once-daily valbenazine met rigorous thresholds for clinician- and self-reported global improvement without compromising their psychiatric stability."

Clinical • Retrospective data • Bipolar Disorder • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Movement Disorders • Psychiatry • Schizophrenia • Suicidal Ideation

Sustained Treatment Response With Long-Term Valbenazine in Patients With Tardive Dyskinesia (ACNP 2022) - P3 | "Background: Valbenazine is a once-daily VMAT2 inhibitor approved for the treatment of tardive dyskinesia (TD), a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics, antiemetics, and other dopamine receptor blocking agents. Post hoc analyses of data from a 48-week, open-label study of once-daily valbenazine showed that the proportion of participants meeting rigorous treatment response thresholds increased over time. By the end of treatment at Week 48, >80% of participants demonstrated robust improvements in TD, as assessed using the AIMS (≥50% improvement), CGI-TD (score ≤2), and PGIC (score ≤2)."

Clinical • CNS Disorders

Pharmacokinetic and Pharmacologic Characterization of the Dihydrotetrabenazine Isomers of Valbenazine and Deutetrabenazine (ACNP 2022) - "Valbenazine is the valine ester of [+]-alpha-dihydrotetrabenazine ([+] α-HTBZ) and is extensively metabolized to its sole HTBZ metabolite, [+]-α-HTBZ, which is believed to be responsible for the majority of the pharmacologic activity of valbenazine. Valbenazine and deutetrabenazine have both been shown in well-controlled trials to be safe and effective for the treatment of TD; however, differences in their pharmacodynamic profiles may have important clinical implications. Deutetrabenazine is metabolized to 4 deuHTBZ stereoisomers, the most abundant of which ([-]-α-deuHTBZ) has negligible interaction with VMAT2 in vitro and appreciable affinity for several off-target receptors- these findings were similar to what has been reported for tetrabenazine. Based on relative potency and abundance, [+]-β-deuHTBZ appears to be the primary contributor to VMAT2 inhibition of deutetrabenazine."

PK/PD data • CNS Disorders

Valbenazine Effects on the Dopamine System in Humans, as Measured by [11C]-PHNO Positron Emission Tomography (PET) (ACNP 2022) - "Valbenazine appears to decrease synaptic dopamine in a dose- and concentration-dependent manner, as indicated by an increase in [11C]-PHNO ΔBPND. The approximately 20-40% [11C] PHNO ΔBPND increase observed in this study is similar to the [11C]-PHNO ΔBPND seen previously following treatment with a tyrosine hydroxylase inhibitor to deplete dopamine (Caravaggio et al, Neuropsychopharmacology 2014;39:2769). Thus, at pharmacological and therapeutic valbenazine doses, biologically meaningful dopamine decreases were observed in humans."

CNS Disorders • Psychiatry

Distinguishing Tardive Dyskinesia From Other Drug-Induced Movement Disorders (Clinical Care Options) - "The presentation will focus on tardive dyskinesia, clinical pearls to distinguish it from other drug-induced movement disorders, and how assessment of the impact of tardive dyskinesia can aid treatment decisions with first-line VMAT2 inhibitor therapy."

Synergy between VMAT2 Inhibitors and Antipsychotics in Animal Models of Schizophrenia - " In one animal model of schizophrenia (conditioned avoidance response [CAR]), rats were dosed with an antipsychotic (risperidone or olanzapine), [+]-alpha-dihydrotetrabenazine ([+]-α-HTBZ, a potent and selective inhibitor of VMAT2), and/or vehicle and tested in 20 trials of foot-shock avoidance. In the CAR model, at subthreshold doses, the mean numbers of escapes for [+]-α-HTBZ alone (0.8 [0.15 mg/kg]) and risperidone alone (0.7 [0.1 mg/kg]) were comparable to vehicle (0.4). CAR suppression increased when subthreshold doses of [+]-α-HTBZ and risperidone were combined (range, 6.5-7.1 escapes), and the results were comparable to the effects at threshold doses for [+]-α-HTBZ alone (4.8-11.4 escapes [0.3 mg/kg]) and risperidone alone (7.2-8.0 escapes [0.3 mg/kg]). This synergistic effect was not due to a drug-drug interaction, as the combination of drugs did not significantly affect the plasma concentration of either agent."

Preclinical • CNS Disorders • Psychiatry • Schizophrenia

Longitudinal Treatment Patterns for Chorea in Patients with Huntington Disease: Data from Enroll-HD (AAN 2022) - "Medications intended for chorea (as indicated in the Enroll-HD Database) were categorized as follows: VMAT2 alone, antipsychotics alone, medications other than VMAT2 inhibitors or antipsychotics (Other), and 2+ different medications from previous 3 categories (Combination)... In this analysis of a natural history database, 36.1% of patients with chorea received medication intended for chorea. Patients generally continued their first-line treatment, but those who switched often received a combination therapy. Continued research is needed to better understand optimal treatment patterns for chorea in patients with HD."

Clinical • CNS Disorders • Genetic Disorders • Huntington's Disease • Movement Disorders

Efficacy of VMAT2 inhibition and synergy with antipsychotics in animal models of schizophrenia. (PubMed, J Pharmacol Exp Ther) - "In combination experiments, synergy was observed: subthreshold doses of RRR-DHTBZ and risperidone or olanzapine produced robust efficacy, and in dose response experiments, RRR-DHTBZ increased the antipsychotic potency in the efficacy models but did not affect weight gain. This study shows that combining these postsynaptic dopaminergic modulators with a presynaptic dopamine modulator (VMAT2 inhibitor) potentiates efficacy synergistically in animal models of schizophrenia without potentiating weight gain. Our data suggest that adding a VMAT2 inhibitor may be a viable therapeutic strategy for reducing antipsychotic side effects by lowering antipsychotic dose while maintaining therapeutic efficacy."

Journal • Preclinical • CNS Disorders • Psychiatry • Schizophrenia

Treatment and Prescription Patterns in Patients with Huntington Disease: Results from a Real-World Claims Analysis (HSG 2021) - " The PearlDiver research database (~53 million patients) was used to identify patients who had ≥2 HD claims (ICD-9-CM 333.4, ICD-10 G10) and ≥12 months of continuous coverage with a medication claim (VMAT2 inhibitor [deutetrabenazine, tetrabenazine] or AP that occurred after HD diagnosis. Differences in prescriber specialty and visit frequency varied between cohorts, suggesting that pharmacotherapy regimens may be impacted by provider specialty."

Clinical • Real-world evidence • CNS Disorders • Genetic Disorders • Huntington's Disease • Movement Disorders • Psychiatry

VMAT2 Inhibitors for the Treatment of Tardive Dyskinesia. (PubMed, Issues Ment Health Nurs) - "Psychiatric nurses are at the forefront of optimizing psychiatric care, including educating patients and caregivers on the risks of antipsychotic-induced movement disorders such as tardive dyskinesia (TD). Given the current pandemic and increase in telehealth, assessing for TD is challenging; however, evaluation can be successfully completed by implementing the best practices described in this paper. Once TD is diagnosed, nurses can reassure patients that safe and effective FDA-approved treatments for TD (e.g., valbenazine) are now available."

Journal • CNS Disorders • Movement Disorders • Psychiatry

Clinician-Reported Patient Awareness of Symptoms and Severity of Tardive Dyskinesia in Patients Prescribed VMAT2 Inhibitors. (PubMed, CNS Spectr) - "In patients prescribed a VMAT2 inhibitor for TD, patient awareness was generally higher in those determined to have moderate-to-severe symptom severity as assessed by the clinician. More research is needed to understand how awareness and severity contribute to TD burden, and whether different treatment strategies are needed based on these factors."

Clinical • Journal • Bipolar Disorder • CNS Disorders • Mood Disorders • Movement Disorders • Psychiatry • Schizophrenia

Understanding the Evolving Continuing Medical Education Needs of Physicians Managing Patients with TD. (PubMed, CNS Spectr) - "Respondents reported moderate familiarity with VMAT2 inhibitor therapies for TD, with self-reported familiarity increasing more among neurologists than psychiatrists since the 2018 study...While both types of specialists would benefit from CME on the topic of TD epidemiology, there is an increased need for CME that includes treatment updates among psychiatrists.Funding. Neurocrine Biosciences, Inc."

Clinical • CME • Journal • CNS Disorders • Movement Disorders • Psychiatry

[VIRTUAL] Clinician-Reported Patient Awareness of Symptoms and Severity of Tardive Dyskinesia in Patients with Schizophrenia/Schizoaffective Disorder Treated with a VMAT2 Inhibitors (SIRS 2021) - "Vesicular monoamine transporter 2 (VMAT2) inhibitors such as valbenazine (approved for treating TD in adults) are recommended as first-line therapies for TD. Discussion In patients with schizophrenia/SZD who were prescribed a VMAT2 inhibitor for TD, clinicians reported that their patients’ awareness of abnormal movements was generally higher in those determined to have moderate-to-severe symptom severity than in those with mild severity. More research is needed to understand how patient awareness is assessed by clinicians, how clinician- versus patient-determined severity contribute to TD burden, and whether different treatment strategies are needed based on these factors."

Clinical • CNS Disorders • Schizophrenia

[VIRTUAL] Clinician-Reported Patient Awareness of Symptoms and Severity of Tardive Dyskinesia in Patients with Schizophrenia/Schizoaffective Disorder Treated with a VMAT2 Inhibitors (SIRS 2021) - "Vesicular monoamine transporter 2 (VMAT2) inhibitors such as valbenazine (approved for treating TD in adults) are recommended as first-line therapies for TD. Discussion In patients with schizophrenia/SZD who were prescribed a VMAT2 inhibitor for TD, clinicians reported that their patients’ awareness of abnormal movements was generally higher in those determined to have moderate-to-severe symptom severity than in those with mild severity. More research is needed to understand how patient awareness is assessed by clinicians, how clinician- versus patient-determined severity contribute to TD burden, and whether different treatment strategies are needed based on these factors."

Clinical • CNS Disorders • Schizophrenia

[VIRTUAL] Chart Extraction/Clinician Survey Shows Symptom Impact and Favorable Treatment Outcomes With VMAT2 Inhibitors in Patients With Tardive Dyskinesia (ASCP 2020) - "Data extracted from patients’ charts included demographics, treatment with a VMAT2 inhibitor (valbenazine, deutetrabenazine, tetrabenazine), antipsychotic treatment, and any documented outcomes. In this real-world sample of patients, TD had negative impacts on >70% of survey respondents. VMAT2 inhibitors were effective in improving TD symptoms and these TD-related impacts, which additionally coincided with improved psychiatric conditions. Clinicians, payers, and professional organizations should consider the symptoms, functional impacts, and treatment outcomes when evaluating TD therapy access and continuation."

Clinical • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Schizophrenia • Substance Abuse