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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 Sclerosis
Icahn School of Medicine at
Mount Sinai
New York, NY
Scott S. Zamvil, MD,
PhD
Professor of Neurology
Department of Neurology
University of California, San
Francisco
San Francisco, CA
Laquinimod: Overview
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Oral therapy
Small molecule: a quinolone-carboxamide
Half-life approximately 70 hours
Dual action:
– Within peripheral immune system
– Within central nervous system (CNS)
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Activity in CNS is relevant to disability
Studied initially in autoimmune
encephalomyelitis (EAE) model in two modes
– Prevention
– Established disease
ALLEGRO and BRAVO
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Phase III trials in relapsing-remitting MS
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Laquinimod 0.6 mg vs placebo
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Primary endpoint = reduction in relapse rate
– ALLEGRO: primary endpoint met
– BRAVO: primary endpoint not met
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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
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Animal model
– Laquinimod given after the onset of
disease (ie, the progressive phase)
prevents axonal transection
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Human trials
– Laquinimod has shown effect on
accumulation of atrophy
CONCERTO Trial
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Ongoing phase III trial in relapsing-remitting MS
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Approximately 1800 patients randomized 1:1:1
–
Laquinimod 0.6 mg
–
Laquinimod 1.2 mg
–
Placebo
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Primary endpoint = disability progression
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The hope is that the higher dose will significantly
reduce disease progression compared with the lower
dose
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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