Oral laquinimod treatment in multiple sclerosis

Abstract

Introduction: Multiple sclerosis (MS) is a chronic disease of the central nervous system, probably of autoimmune origin. Its early treatment with interferon beta or glatiramer acetate reduces the number of exacerbations, slows disability progression and improves the quality of life, but these treatments are only partially effective and require parenteral administration.

Aim: To review current experience with laquinimod as a novel immunomodulatory therapy for relapsing-remitting MS (RRMS).

Development: Laquinimod is a new quinolone-carboxamide that has shown efficacy in various animal models of autoimmune disease, including MS. Laquinimod shows immunomodulatory effects, probably through Th1/Th2 shift, but does not lead to immunosuppression. Laquinimod is metabolised primarily by the CYP3A4 enzyme in the liver. Phase II studies in RRMS demonstrate a dose-response effect on disease activity, measured by the number of active lesions on brain magnetic resonance imaging, and show favourable tolerability and safety based on clinical and laboratory indicators. Two Phase III studies currently in progress are evaluating the efficacy of laquinimod 0.6 mg/day in RRMS. The drug was granted a fast track review by the FDA in 2009.

Conclusions: Laquinimod is a novel, orally administered immunomodulator that has advanced to phase III study, a pre-submission stage to the regulatory agencies, and may become an alternative to the current injectable first-line treatments for RRMS.