Background: Long-acting injectable antipsychotic (LAI) treatment is associated with improved adherence and reduced relapse and hospitalization rates, compared with oral antipsychotics, in patients with schizophrenia. TV-46000, an LAI formulation of risperidone, is approved for the treatment of schizophrenia in adults. TV-46000 administered once monthly (q1m) and once every 2 months (q2m) has previously been shown to be effective and safe in patients with schizophrenia in the phase 3 studies, RISE and SHINE. Here, the effect of long-term treatment with TV-46000 on psychopathological symptoms and severity of illness was evaluated.
Methods: In RISE, patients were stabilized on oral risperidone for 12 weeks before randomization to subcutaneous treatment with TV-46000 q1m, q2m, or placebo (1:1:1) until study endpoint. Patients who successfully completed RISE (placebo and TV-46000 rollover cohorts) and newly recruited patients (de novo cohort) were eligible to enroll in SHINE to receive TV-46000 q1m or q2m for up to 56 weeks. Symptom severity was evaluated with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions-Severity (CGI-S) scale, and the Clinical Global Impressions-Improvement (CGI-I) scale, as prespecified exploratory endpoints from the RISE and SHINE studies.
Results: Overall, 543 adult patients were enrolled in RISE (TV-46000 q1m, n = 183; q2m, n = 179; placebo, n = 181) and 333 in SHINE (TV-46000 q1m, n = 173 and q2m, n = 160; source groups: de novo, n = 106; placebo rollover, n = 55; TV-46000 rollover, n = 172). In RISE, PANSS total scores decreased after randomization to end of treatment (EoT) for TV-46000 (least squares mean [LSM] change [SE], q1m: -3.5 [0.69]; q2m, -4.9 [0.73]), but increased for placebo (1.1 [0.86]; P < 0.0001 for both TV-46000 q1m and q2m versus placebo). Corresponding changes from baseline to last assessment (LA) were -0.9 (0.97) for q1m, -0.2 (0.99) for q2m, and 7.4 (0.99) for placebo; P < 0.0001 for both versus placebo. Similar results were seen for the PANSS positive and general psychopathology subscales (P < 0.001 for both TV-46000 q1m and q2m versus placebo). These symptom improvements were maintained or improved in the TV-46000 q1m and q2m groups in SHINE, with notable improvements observed in patients without prior TV-46000 exposure. Similar results were observed in RISE and SHINE when PANSS scores were categorized by Marder factors of schizophrenia symptoms. CGI-I scores at EoT and LA were significantly better with TV-46000 than with placebo in RISE (LSM at EoT and LA: 3.3 and 3.6 for TV-46000 q1m, 3.2 and 3.6 for q2m; 3.9 and 4.4 for placebo, respectively [P < 0.0001 versus placebo]). These scores were maintained in the TV-46000 groups in SHINE, with larger improvements seen in the de novo cohort than in the placebo rollover and TV-46000 rollover cohorts.
Conclusions: Treatment with TV-46000 provided sustained overall symptom improvement in the RISE and SHINE studies in patients with schizophrenia who were stabilized on oral risperidone.
Clinical trials registration: RISE (ClinicalTrials.gov identifier: NCT03503318) and SHINE (ClinicalTrials.gov identifier: NCT03893825).
TV-46000 is an antipsychotic medicine to treat schizophrenia in adults. It is injected under the skin once monthly or once every 2 months. TV-46000 was previously tested in two clinical trials, RISE and SHINE. In RISE, patients first took pills and then received TV-46000 or inactive treatment (placebo). Patients treated with TV-46000 had a longer period without schizophrenia symptoms returning than those who took placebo treatment. New patients and patients who finished RISE were allowed to participate in the SHINE study. In SHINE, patients were regrouped to receive TV-46000. Results showed that long-term treatment with TV-46000 was safe. This report used existing data from the RISE and SHINE studies to see if TV-46000 improved schizophrenia symptoms and disease severity. In RISE, schizophrenia symptoms improved with TV-46000 but worsened with placebo. Symptoms were further improved in patients who continued taking TV-46000 in SHINE. The overall disease severity was also improved in RISE and SHINE.
© 2025. The Author(s).