Development of Laquinimod for Relapsing–Remitting Multiple Sclerosis

Abstract

Laquinimod, a quinoline-3-carboxamide derivative, is a new, once-daily oral immunomodulatory therapy in development for the treatment of relapsing–remitting multiple sclerosis (MS). It has demonstrated efficacy in both acute and chronic experimental allergic encephalitis and in animal models of other inflammatory autoimmune diseases. It appears to act, in part, by shifting the immune response from a Th1 to a Th2 response and does not act through nonspecific immunosuppression. In Phase II studies in relapsing forms of MS, laquinimod brought about a 60% decrease in the cumulative number of gadolinium-enhancing lesions and a 33% decrease in relapse rates. In Phase II studies it was safe and well-tolerated. The most common laboratory abnormalities were a transient rise in alanine aminotransferase and C-reactive protein that returned to normal values despite continued therapy. There was no evidence of a proinflammatory effect. Phase III clinical trials for registration are in progress. Laquinimod may find use as a first-line agent in the treatment of relapsing forms of MS.