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Laquinimod in the treatment of multiple sclerosis: a review of the data so far

Authors Thöne J, Linker R

Received 14 November 2015

Accepted for publication 2 February 2016

Published 14 March 2016 Volume 2016:10 Pages 1111—1118

DOI https://doi.org/10.2147/DDDT.S55308

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Wei Duan


Jan Thöne,1 Ralf A Linker2

1Department of Neurology, University Hospital Essen, Essen, 2Department of Neurology, University Hospital of Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany

Abstract: Laquinimod (ABR-215062) is a new orally available carboxamide derivative, which is currently developed for relapsing remitting (RR) and chronic progressive (CP) forms of multiple sclerosis (MS; RRMS or CPMS) as well as neurodegenerative diseases. Its mechanism of action may comprise immunomodulatory effects on T-cells, monocytes, and dendritic cells as well as neuroprotective effects with prominent actions on astrocytes. Laquinimod was tested in Phase II and III clinical trials in RRMS at different dosages ranging from 0.1 to 0.6 mg/day. The compound was well tolerated, yet at the dosages tested only led to moderate effects on the reduction of relapse rates as primary study endpoint in Phase III trials. In contrast, significant effects on brain atrophy and disease progression were observed. While there were no significant safety signals in the clinical trials, the Committee for Medicinal Products for Human Use (CHMP) refused marketing authorization for RRMS based on the assessment of the risk–benefit ratio with regard to data from animal studies. At present, the compound is further tested in RRMS as well as CPMS and Huntington’s disease at different concentrations. Results from these trials will further inform about the clinical benefit of laquinimod in patient cohorts with a persisting, but still insufficiently met need for safe and at the same time effective oral compounds with neuroprotective effects.

Keywords: neuroprotection, ABR-215062, axonal damage, demyelination

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