1. 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

2. 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

3. 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

4. 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

5. 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 NCT

6. 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