Glatiramer acetate (GA) seems to affect immune cells in an antigenic specific way, and could be considered as an example of a therapeutic vaccination, as opposed to the prophylactic vaccinations commonly used for infectious diseases. The first human use of GA was in three patients with acute disseminated encephalomyelitis and four in the terminal stages of multiple sclerosis (MS). Cross-sectional analysis of data from the extended, open label follow-up of the US trial investigated the consequences of long-term GA treatment on several magnetic resonance imaging (MRI) markers of MS activity and disease burden. As GA has unique mechanisms of action, which differs from those of other MS disease therapies, use in combination with other agents might produce additive or synergistic therapeutic effects and better efficacy. The effects of oral GA were extensively studied in both rodents and primates in acute and chronic relapsing experimental autoimmune encephalomyelitis (EAE) models.

Laquinimod is rapidly absorbed following oral administration with bioavailability of 82%-95%. Two Phase 2 clinical trials were conducted with laquinimod. Both demonstrated a reduction in the frequency of gadolinium (Gd)-enhancing lesions and relapses in patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). Laquinimod was well tolerated in both Phase 2 trials with few side effects. There was no difference in the overall number of adverse events (AEs) or serious adverse events (SAEs) between the placebo and laquinimod groups. Laquinimod effectively ameliorates both acute and chronic experimental autoimmune encephalomyelitis (EAE) decreasing both demyleination and axonal loss. Laquinimod may have protective effects on axonal integrity beyond that associated with decreased inflammation. Laquinimod has no immuno suppressive effects in animal models or in human studies, and does not decrease the ability of animals to mount a cellular or humeral immune response. The safety profile of laquinimod appears quite favorable.