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