Laquinimod, a Once-Daily Oral Drug in Development for The Treatment of
Relapsing–Remitting Multiple Sclerosis
Stephen Krieger, MD Assistant Professor of Neurology
and Medical Director
The Corinne Goldsmith Dickinson Center for
Multiple SclerosisIcahn School of Medicine at
Mount SinaiNew York, NY
Scott S. Zamvil, MD, PhD
Professor of NeurologyDepartment of Neurology
University of California, San Francisco
San Francisco, CA
Laquinimod: Overview Oral therapy Small molecule: a quinolone-carboxamide Half-life approximately 70 hours Dual action:
– Within peripheral immune system – Within central nervous system (CNS)
Activity in CNS is relevant to disability Studied initially in autoimmune
encephalomyelitis (EAE) model in two modes– Prevention– Established disease
ALLEGRO and BRAVO
Phase III trials in relapsing-remitting MS Laquinimod 0.6 mg vs placebo Primary endpoint = reduction in relapse rate
– ALLEGRO: primary endpoint met– BRAVO: primary endpoint not met
Both ALLEGRO and BRAVO showed greater efficacy for reducing disability progression and atrophy than for reducing relapse rate– Unique observation because all other MS drugs
have shown greater efficacy for relapse rate
Laquinimod and Atrophy
Animal model– Laquinimod given after the onset of
disease (ie, the progressive phase) prevents axonal transection
Human trials– Laquinimod has shown effect on
accumulation of atrophy
CONCERTO Trial Ongoing phase III trial in relapsing-remitting MS Approximately 1800 patients randomized 1:1:1
– Laquinimod 0.6 mg– Laquinimod 1.2 mg– Placebo
Primary endpoint = disability progression The hope is that the higher dose will significantly
reduce disease progression compared with the lower dose
ClinicalTrials.gov number NCT01707992
Laquinimod: Areas of Future Study Combination therapy
– Pair with disease-modifying therapy that has strong efficacy in relapse rate reduction
– Draw on lessons learned in SENTINEL and CombiRx
Progressive MS– Trial endpoints of disability progression and
atrophy are particularly relevant for progressive MS
– ALLEGRO and BRAVO showed efficacy of laquinimod in patients who progressed without relapse
– Area of unmet need