TV-46000, A Long-Acting Subcutaneous Antipsychotic Agent, Demonstrated Improved Patient-Centered Outcomes in Patients with Schizophrenia

Leslie Citrome,1 Mark Suett,2 Kelli R Franzenburg,3 Roy Eshet,4 Anna Elgart,4 Glen L Davis 3rd,5 Eran Harary,4 Orna Tohami,4 Marko A Mychaskiw,6 John M Kane7– 9 1Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, NY, USA; 2Global Medical Affairs, Teva UK Limited, Harlow, UK; 3Global Medical Affairs, Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, USA; 4Innovative Medicines, Global Clinical Development, Teva Pharmaceutical Industries Ltd, Netanya, Israel; 5Global Clinical Operations, Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, USA; 6Global Health Economics and Outcomes Research, Teva Branded Pharmaceutical Products R&D, Inc, West Chester, PA, USA; 7Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA; 8Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; 9Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY, USACorrespondence: Leslie Citrome, Department of Psychiatry and Behavioral Sciences, New York Medical College, 40 Sunshine Cottage Road, Valhalla, NY, 10595, USA, Email nntman@gmail.comBackground: TV46000 is a long-acting subcutaneous antipsychotic (LASCA) formulation of risperidone approved for the treatment of schizophrenia in adults.Methods: The RISE study (NCT03503318) compared TV-46000 once monthly (q1m) and once every 2 months (q2m) with placebo (1:1:1) in patients with schizophrenia who underwent stabilization on oral risperidone. The SHINE study (NCT03893825) evaluated the long-term safety, tolerability, and effectiveness of TV-46000 in patients who completed RISE without relapse (rollover; placebo rollover randomized [1:1] to q1m or q2m; TV-46000 rollover continued assigned treatment) or who were newly recruited (de novo; randomized [1:1] to q1m or q2m after oral stabilization). Patient-centered outcomes included the Schizophrenia Quality of Life Scale (SQLS), the 5-Level EuroQoL 5-Dimensions Questionnaire (EQ-5D-5L), the Personal and Social Performance Scale (PSP), and the Drug Attitudes Inventory 10-item version (DAI-10).Results: In RISE, SQLS least-squares mean changes (SE) improved to last assessment (LA) for TV-46000 q1m (– 4.15 [1.03]) and q2m (– 3.28 [1.06]) but worsened for placebo (1.75 [1.07]; P< 0.001 for both). PSP, EQ5D-5L, and DAI-10 showed similar trends. In SHINE, SQLS decreased (improved) at LA for both TV-46000 q1m (− 0.43 [0.98]) and q2m (− 2.16 [0.98]); reductions were observed in the de novo (q2m only) and placebo rollover (q1m and q2m) cohorts, but not for the TV46000 rollover cohort. Results for PSP, EQ5D-5L, and DAI-10 were consistent with those reported in the RISE study.Conclusion: Improvements in patient-centered outcomes were observed across cohorts, with the largest improvements observed for patients who began TV-46000 during SHINE (ie, de novo and placebo rollover cohorts), while gains made during RISE were minimally improved or maintained in the TV-46000 rollover cohort, indicating the benefit of uninterrupted TV-46000 treatment. These data support the effectiveness of TV-46000 to improve patient-centered outcomes in patients with schizophrenia.Plain Language Summary: RISE and SHINE were clinical studies where patients with schizophrenia received TV-46000. TV-46000 is injected under the skin once monthly or once every 2 months to treat schizophrenia in adults. In RISE, patients took pills for the first 3 months, and then received injections under the skin. Some patients received inactive (placebo) injections. Comparing results among groups showed the effectiveness and side effects of TV-46000. Patients who completed RISE could continue into SHINE. SHINE included patients who had not been part of RISE as well. All patients received TV-46000 in SHINE to see if results were the same long term. This report summarizes the results of patient-centered outcomes. These included measures of quality of life and attitudes toward the medicine. In RISE, quality of life and attitudes toward the medicine improved with TV-46000, but worsened with placebo. In SHINE, the patient-centered outcomes also improved. The largest improvements were for patients who began taking TV-46000 during SHINE. This analysis showed that there is a benefit in taking TV-46000 for longer times without breaks. It also showed that TV-46000 improves quality of life and attitudes toward the medicine.Keywords: schizophrenia, long-acting injectable, risperidone, patient-centered outcomes