Subcutaneous risperidone delays impending relapse in schizophrenia

Subcutaneous injection of risperidone QM or Q2M (TV-46000) has been shown to significantly delay impending relapse in patients with schizophrenia in the phase III RISE study.

“Nonadherence during long-term treatment with oral medication is one of the most persistent and challenging therapeutic issues in schizophrenia,” noted the researchers. “Treatment with long-acting injectable [LAI] antipsychotics has been shown to improve adherence and reduce relapse and hospitalization vs oral antipsychotics.” Additionally, subcutaneous formulations are often preferred by patients and may further improve treatment adherence. [Lancet Psychiatry 2023;doi:10.1016/S2215-0366(23)00288-2]

TV-46000 is a long-acting, subcutaneous antipsychotic treatment that combines risperidone and a copolymer-based drug delivery technology in a suspension in a prefilled syringe. Its efficacy and safety were evaluated in the phase III RISE study, which consisted of two treatment stages: a 12-week, open-label stabilization phase with oral risperidone (stage 1), and an open-ended, randomized, double-blind, placebo-controlled, relapse-prevention phase with subcutaneous TV-46000 (stage 2) at 69 clinical sites across the US and Bulgaria. Among 1,267 patients screened, 544 (mean age, 49.3 years; male, 61 percent) were randomized 1:1:1 to receive subcutaneous TV-46000 QM, TV-46000 Q2M, or placebo.

Time to impending relapse was significantly prolonged by 5 times with TV-46000 QM (hazard ratio [HR], 0.2; 95 percent confidence interval [CI] 0.109–0.367; p<0.0001) and by 2.7 times with TV-46000 Q2M (HR, 0.375; 96 percent CI, 0.227–0.618; p<0.0001) vs placebo. Additionally, the risk of relapse was reduced by 80.0 percent and 62.5 percent vs placebo, respectively.

“Although there was a numerical difference between the two TV-46000 regimens, it must be kept in mind that the CIs of the HRs for time to impending relapse overlapped, and that the RISE study was not powered to detect differences between TV-46000 treatment groups for time to impending relapse or any other efficacy endpoint,” pointed out the researchers.

The efficacy of TV-46000 vs placebo was similar to that shown with intramuscular LAI antipsychotics (eg, aripiprazole, paliperidone, risperidone), according to studies with a similar design to the RISE trial and a network meta-analysis. [J Clin Psychiatry 2012;73:617-624; Am J Psychiatry 2021;178:424-436]

“Subcutaneous TV-46000 delayed time to relapse, facilitates convenient administration, and does not require oral supplementation, loading doses, or booster injections,” highlighted the researchers.

The most frequently reported treatment-related adverse events (TEAEs) were injection site nodules (7 percent for TV-46000 Q1M, 7 percent for TV-46000 Q2M, 3 percent for placebo), weight increase (4 percent, 6 percent, and 2 percent, respectively), and extrapyramidal disorder (5 percent, 3 percent, and 0 percent, respectively). The safety profile of TAV-46000 was consistent with other approved formulations of risperidone, without any new safety signals.

TV-46000 has two dosing intervals (QM and Q2M) and can be administered subcutaneously into multiple injection sites, including the abdomen and upper arm. “The availability of a range of treatment regimens will allow for better individualization to meet patients’ preferences during long-term maintenance treatment of schizophrenia,” commented the researchers. “These treatment options might increase adherence and consequently alleviate symptoms, prevent relapse, and improve quality of life.”

Based on the positive results of RISE and SHINE (second phase III trial), TV-46000 received US FDA approval in April 2023 for treatment of schizophrenia in adults. [https://www.tevapharm.com/news-and-media/latest-news/teva-and-medincell-announce-fda-approval-of-uzedy-risperidone-extended-release-injectable-suspension-/]