In RISE, TV46000 once monthly (q1m) or once every 2 months (q2m) significantly extended time to impending schizophrenia relapse. The current study (SHINE, NCT03893825) evaluated the long-term safety, tolerability, and effect of TV46000.

Patients completing RISE without relapse (rollover) or newly recruited (de novo) were eligible. The de novo and placebo rollover cohorts were randomized 1:1 to q1m or q2m for ≤56 weeks; the TV46000 rollover cohort continued assigned regimen. Exploratory efficacy endpoints included time to impending relapse and patient centered outcomes (PCOs) including Schizophrenia Quality of Life Scale (SQLS).

334 patients were randomized and received TV46000 q1m (n=172) or q2m (n=162), for 202.3 patient-years [PY] of TV-46000 treatment. Treatment-emergent adverse events (AEs) reported for ≥5% of patients were: overall–injection site pain (event rate/100 PY, n [%]; 23.23, 16 [5%]); de novo (n=109)–injection site pain (56.10, 11 [10%]), injection site nodule (16.03, 6 [6%]), blood creatine phosphokinase increased (16.03, 8 [7%]), urinary tract infection (10.69, 7 [6%]); placebo rollover (n=53)–tremor (18.50, 5 [9%]); TV46000 rollover (n=172)–headache (7.97, n=8 [5%]). Serious AEs reported for ≥2 patients were worsening schizophrenia and hyperglycemia. Kaplan– Meier estimates for remaining relapse-free at week 56 were 0.98 (2% risk; q1m) and 0.88 (12%; q2m). SQLS improved for q1m (least-squares mean change [SE], − 2.16 [0.98]) and q2m (− 0.43 [0.98]); other PCOs (5Level EuroQoL 5Dimensions Questionnaire, Personal and Social Performance Scale, Drug Attitudes Inventory 10-item version) remained stable.

TV-46000 had a favorable long-term benefit–risk profile in patients with schizophrenia.

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Study Registration Number: NCT03893825

Valbenazine and deutetrabenazine (vesicular monoamine transporter 2 inhibitors) are approved for tardive dyskinesia (TD) treatment in adults. To prevent potential drug-drug interactions (DDIs), valbenazine labeling recommends doses 40 mg/day when taking strong CYP3A4 or CYP2D6 inhibitors and avoidance of strong CYP3A4 inducers and monoamine oxidase inhibitors (MAOIs). Deutetrabenazine labeling recommends doses ≤36-mg/day when taking strong CYP2D6 inhibitors and avoidance of MAOIs. This study estimated proportions of patients with TD at risk of DDIs with valbenazine/deutetrabenazine in real-world practice.

Patients aged ≥18 years with TD and ≥1 antipsychotic claim(s) and no valbenazine/ deutetrabenazine claims ≥3 months prior and ≥12 months after diagnosis were identified in the Symphony Health Sciences database (US-based medical, hospital, and pharmacy claims database). Proportions of patients meeting valbenazine/deutetrabenazine concomitant medication labeling restrictions were summarized descriptively.

14,264/66,046 patients with TD met inclusion criteria. Proportions of patients at potential risk of DDIs were lower with deutetrabenazine ≤36 mg/day (0.2%) and >36 mg/day (21%) versus valbenazine 40 mg/day (4.4%; 22-times difference) and >40 mg/day (28%; 1.3-times difference). Across age groups, underlying conditions (major depressive, mood, and bipolar disorders; schizophrenia), and payer types, proportions of patients at potential risk of DDIs were lower with deutetrabenazine ≤36 mg/day (0.0%– 0.5%) and >36 mg/day (14%– 30%) versus valbenazine 40 mg/day (3%– 5%; 8.0- to >40.0times difference) and >40 mg/day (22%– 35%; 1.2- to >1.5-times difference).

Estimated proportions of patients with TD at potential risk of DDIs was lower with deutetrabenazine versus valbenazine overall and across age, underlying conditions, and payer types.

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Tardive dyskinesia (TD) is associated with antipsychotic (AP) use and management includes antipsychotic (AP) dose modification/discontinuation, often leaving underlying psychiatric conditions undertreated. Deutetrabenazine (DTBZ) is a vesicular monoamine transporter type 2 inhibitor (VMAT2i) approved to treat TD and Huntington disease– associated chorea. AP and VMAT2i treatment patterns post-TD diagnosis are unclear.

Patients aged ≥18 years, newly diagnosed with TD (July 2019– June 2022), with ≥1 AP and no VMAT2i claims pre-index were identified from the Symphony Health Solutions Integrated Dataverse (medical, hospital, and prescription claims across all US payer types). Patients were grouped into DTBZ (≥1 DTBZ claim within ≤6 months post-diagnosis) and non-VMAT2i groups, and further by stable DTBZ dose (for ≥60 days). The index date was the first DTBZ claim (DTBZ group) or the difference between TD diagnosis and first DTBZ claim (of the matched patient) added to TD diagnosis (non-VMAT2i group).

Among 18,375 patients meeting inclusion criteria, 587 (3%) received DTBZ (292 stable-dose DTBZ), 676 (4%) received a different VMAT2i, and 17,112 (93%) had no VMAT2i claims. Among propensity score-matched patients with ≥1 AP claim pre- and post-index (326 DTBZ, 627 non-VMAT2i), pre-index mean AP proportions of days covered (PDCs) were similar between DTBZ (86%), stable-dose DTBZ (86%), and non-VMAT2i (83%) groups. Mean PDCs decreased post-index for DTBZ (86% to 85%) and non-VMAT2i (83% to 81%) groups, but increased for the stable-dose DTBZ group (86% to 88%). While these changes were small, post-index mean PDCs were significantly greater (versus non-VMAT2i) in the DTBZ (5% difference; P=.030) and stable-dose DTBZ (9%; P=.001) groups. Similar proportions of patients in the DTBZ (20%) and non-VMAT2i (20%) groups discontinued APs (ie, no AP claims within ≤6 months post-index). Proportions of patients with AP restarts (7%– 8%) and dose decreases (13%– 17%) were also similar between DTBZ, stable-dose DTBZ, and non-VMAT2i groups. Proportions of patients (16%– 18%) with AP dose increases were similar between DTBZ and non-VMAT2i groups, but significantly greater in the stable-dose DTBZ group (21%) vs non-VAMT2i (P=.02).

AP adherence was significantly, though not substantially, greater for DTBZ versus non-VMAT2i groups. These results suggest that DTBZ, when titrated to a stable/optimal dose, allows flexibility in treating underlying psychiatric conditions.

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Healthcare professionals (HCPs) face unique challenges when managing patients with schizophrenia. Educational initiatives targeting common clinical dilemmas encountered by clinicians, including partial or nonadherence, may alleviate knowledge gaps and clarify the role of long-acting injectable antipsychotic agents (LAIs) in treating this population.

4 experts in schizophrenia management used empirical evidence to identify 11 key clinical dilemmas where LAIs may be useful. These experts then developed a heuristic, educational tool (S.C.O.P.E.™: Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement) based on empirical evidence and expert opinion for clinicians to use when encountering similar scenarios to optimize schizophrenia care.

S.C.O.P.E.™ is a freely-available resource comprising an interactive digital platform providing educational materials for HCPs involved in continued care for patients with schizophrenia. S.C.O.P.E.™ provides HCPs with considerations in common clinical scenarios met in inpatient and outpatient settings, as well as questions to consider when patients present to the emergency department. The potential usefulness of LAIs is explored in each scenario. Clinical education videos prepare nurse practitioners, social workers, and case managers to address patient concerns and communicate the benefits of LAI treatment. S.C.O.P.E.™ will not replace clinical judgment, guidelines, or continuing medical education, and is not a platform for recording patient-level data, nor intended for payer negotiations or access-related questions by HCPs.

S.C.O.P.E.™ is an educational tool for HCPs to use alongside standard psychiatric evaluations to improve understanding of how to manage common clinical dilemmas when treating patients with schizophrenia and the role of LAIs in schizophrenia management.

Teva Branded Pharmaceutical Products R&D, Inc.

Healthcare professionals (HCPs) face unique challenges when managing patients with schizophrenia. Educational initiatives targeting common clinical dilemmas encountered by clinicians, such as unfamiliarity with prescribing information for long-acting injectable antipsychotics (LAIs), may assist clinicians when treating patients with schizophrenia.

Four experts in schizophrenia management used empirical evidence to identify 11 key clinical dilemmas where LAIs may be useful. These experts then developed a heuristic, educational tool (S.C.O.P.E.™: Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement) based on empirical evidence and expert opinion for clinicians to use when encountering similar scenarios to optimize schizophrenia care. S.C.O.P.E.™ also includes supportive elements such as an LAI selector.

S.C.O.P.E.™ is a freely available resource comprising an interactive digital platform providing educational materials for HCPs involved in continued care for patients with schizophrenia. To acquaint HCPs with characteristics of common LAIs used in schizophrenia treatment, S.C.O.P.E.™ offers a selector that filters LAIs by approved indication(s), initiation regimen, reconstitution, dosing strengths and frequency, injection volumes and routes, and supply and storage information based on approved product labels. The LAI selector does not provide LAI safety and efficacy data, so HCPs should visit individual product websites for this information. Therefore, S.C.O.P.E.™ will not replace clinical judgment, guidelines, or continuing medical education, and is not a platform for recording patient-level data, nor intended for payer negotiations or access-related questions by HCPs.

S.C.O.P.E.™ is an educational tool for HCPs to use alongside standard psychiatric evaluations to improve understanding of how to manage common clinical dilemmas when treating patients with schizophrenia, the role of LAIs in schizophrenia management, and the product characteristics of available LAIs.

Teva Branded Pharmaceutical Products R&D, Inc.