Laquinimod in the treatment of relapsing remitting multiple sclerosis

ABSTRACT

Introduction: Laquinimod is a new once-daily oral administrable agent, which is under investigation in a phase 3 clinical trial for relapsing remitting multiple sclerosis (RRMS) and in a phase 2 clinical trial for primary progressive MS (PPMS).

Areas covered: The pharmacokinetic, pharmacodynamic and the safety profiles of laquinimod are covered in this review. In preclinical studies, the ability to prevent both experimental autoimmune encephalomyelitis and experimental autoimmune neuritis has been demonstrated. Reduced cell infiltration, demyelination, axonal damage and a shift of T-helper cell responses have been shown. Accordingly, in human studies, a decrease of pro-inflammatory and an increase of anti-inflammatory cytokines have been measured and a significant reduction of disease progression and a decrease in brain volume loss has been demonstrated. During all clinical studies a favorable safety profile was observed for 0.6mg laquinimod. New information about cardiovascular events is prompting the discontinuation of higher dosing regimens in both ongoing trials.

Expert opinion: Laquinimod is a first in class oral agent with high potential to reduce disease progression in RRMS and PPMS. Owing to its favorable safety profile, a combination with 0.6mg laquinimod and other disease modifying therapies could be an option in future MS therapy.

KEYWORDS:

• Cytokines
• demyelination
• immunomodulation
• laquinimod
• neuroprotection
• MRI

Declaration of interests

U Hainke has received travel support from Biogen Idec and Novartis. K. Thomas has received has received honorarium from Novartis, Bayer and Biogen idec. T. Ziemssen is on the scientific advisory board for Bayer Healthcare, Biogen Idec, Novartis, Merck-Serono, Teva, Genzyme, and Synthon; has received speaker honorarium from Bayer Healthcare, Biogen Idec, Genzyme, MSD, GSK, Novartis, Teva, Sanofi, and Almirall; and has received research support from Bayer Halthcare, Biogen Idec, Genzyme, Novartis, Teva, and Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.