Olanzapine for Extended-Release Injectable Suspension (TV-44749) for Subcutaneous Use Is Designed for Sustained Efficacy and to Eliminate Causes of Post-injection Delirium/Sedation Syndrome: In Vitro and Clinical Data
Use of intramuscular long-acting injectable (LAI) olanzapine is limited due to a boxed warning for post-injection delirium/sedation syndrome (PDSS) and associated REMS. PDSS may arise from vessel injury during intramuscular injection, resulting in rapid dissolution of olanzapine and significant increases in plasma concentration.
TV-44749 is a once-monthly, subcutaneous, extended-release injectable olanzapine that utilizes an innovative copolymer drug delivery technology to ensure controlled olanzapine release over a 1-month period. TV-44749’s subcutaneous administration route and formulation were designed to provide sustained efficacy and eliminate causes of PDSS. Subcutaneous tissue is less vascular than muscle tissue; therefore, inadvertent intravascular penetration is less likely. Moreover, if intravascular penetration occurs, TV-44749 copolymers are expected to precipitate instantly in contact with plasma forming a depot, which entraps olanzapine particles preventing rapid dissolution. Solubility and in vitro release studies of olanzapine in human plasma explored the risk of PDSS following TV-44749 injection versus the currently marketed intramuscular olanzapine LAI. The phase 1 study evaluated TV-44749’s pharmacokinetic characteristics.
TV-44749 maintained controlled-release properties without any burst in olanzapine concentrations in plasma. The benefit of TV-44749’s administration and formulation is seen in phase 1 and 3 studies where there have been no suspected or confirmed PDSS events. SOLARIS (NCT05693935), an ongoing randomized, double-blind, placebo-controlled, phase 3 study, assessed the efficacy, safety, and tolerability of TV-44749 in adults with schizophrenia (n=675). In Period 1 (8-week acute treatment period), alongside no reported PDSS events (>3217 active injections, 08/2024), TV-44749 was well tolerated with a systemic safety profile consistent with approved olanzapine formulations.
