Effects of Long-Term Treatment with TV-46000 on Symptom Improvement Over Time in Stabilized Patients with...

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.

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.

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.

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.

RISE (ClinicalTrials.gov identifier: NCT03503318) and SHINE (ClinicalTrials.gov identifier: NCT03893825).