(P149) GLATIRAMER ACETATE (GA) LONG-ACTING INJECTION (GA DEPOT) EFFECT IN A MOUSE MODEL OF IBD

Inflammatory bowel disease (IBD) encompasses a group of inflammatory disorders affecting the gastrointestinal tract, characterized by intestinal inflammation and mucosal injury. The pathogenesis of IBD is largely driven by dysregulated immune responses, particularly involving CD4+ Th1 cells, and an imbalance between pro-inflammatory and anti-inflammatory pathways. A Widely used animal-based IBD model is the dextran sulphate sodium (DSS)-induced colitis. Glatiramer Acetate (GA) which is a known immunomodulator, is approved for treatment of Relapsing forms of Multiple Sclerosis and known for its excellent safety profile.   In this model, daily administration of GA at a dose of 2 mg/mouse has demonstrated significant therapeutic effects in mitigating DSS-induced colitis¹. GA Depot, a long-acting formulation of GA designed for parenteral administration every 28 days, is available either as a lyophilized powder for reconstitution and intramuscular injection or as a ready-to-use medium chain triglyceride (MCT) suspension for subcutaneous self-injection. Two studies were conducted to assess the efficacy of a single administration of GA Depot in DSS-induced colitis in mice. 

The objective of the first study was to evaluate the effects of different doses and solvents of GA Depot. The second study aimed to compare the efficacy of GA Depot with that of infliximab (IFX), an established treatment for IBD².

In the first study, seven groups were included: naïve controls, untreated controls and groups receiving GA Depot at 2 or 10 mg administered intramuscularly (IM) or subcutaneously (SC), with the formulation suspended in either water for injection or medium chain triglyceride (MCT). The second study included naïve and untreated controls, GA Depot at 2 and 10 mg (suspended in MCT and administered SC), and Infliximab (IFX) administered intravenously. All treatments were administered once on day 1 of the study. Outcome measures included the daily activity index (DAI), which assessed changes in body weight, rectal bleeding, and stool consistency, as well as colon length and histopathological scoring.

In both studies, all treatment groups demonstrated beneficial effects on DSS-induced colitis, including reductions in DAI, improved histopathological scores and less colon shortening compared to untreated controls. GA Depot, administered SC in MCT at doses of 2 or 10 mg, exhibited comparable efficacy to IFX.

The results indicate that GA Depot shows similar efficacy to IFX, a widely used treatment for Crohn's Disease and ulcerative colitis. These findings provide proof of concept for the potential future clinical use of GA Depot in these indications with expected excellent safety profile based on the current clinical experience with GA.

< !  1) Aharoni et al., (2006), JPET 318:68–78

< !  2)  Leputsoet. al., (2013), Digestive and Liver Disease 45: 1017-1021