Clinical Efficacy of Laquinimod for the Treatment of Multiple Sclerosis; Pooled Analyses from the ALLEGRO and BRAVO Phase III Trials (S01.007)

Objective: The current report provides detail on pooled analyses assessing the effect of laquinimod on relapse, disability, and brain atrophy measures from the recently completed phase III trials ALLEGRO and BRAVO. Background Laquinimod is an oral, CNS acting immunomodulator in development for the treatment of multiple sclerosis. Its impact on disability progression and brain atrophy, two indices of longterm outcome for patients with multiple sclerosis (MS) are being studied in its phase III trials. Design/Methods: MS patients (N=2437) were randomized to laquinimod (n=984) or placebo (n = 1006). In both trials, patients underwent neurological examinations including the Expanded Disability Status Scale (EDSS) at screening, baseline visits and every 3 months thereafter until discontinuation or study end at 24 months. MRI scans were taken at screening, baseline, month 12 and month 24 visits. Annualized relapse rate was the primary endpoint and the risk to 3 month confirmed disability progression was a secondary endpoint. Percent change in brain volume using the SIENA technique was an exploratory endpoint in the ALLEGRO trial and a secondary endpoint in the BRAVO trial. Results: Pooled analyses on annualized relapse rate found that laquinimod reduced relapse rate by 21.4% (.30 ARR for laquinimod vs .38 for placebo patients, p = 0.0005). Pooled analyses on the risk to confirmed disability progression sustained for 3 months found laquinimod significantly reduced the risk compared to placebo 34.2% (p = 0.0017). Using a more stringent criteria of sustained disability for 6 months, there was a significant reduction by laquinimod, (46%, p Conclusions: Laquinimod slows disability progression and brain atrophy with a good safety profile suggesting it may have an important role in improving longterm outcomes in MS patients. Supported by: Teva Pharmaceuticals Israel. Disclosure: Dr. Vollmer has received personal compensation for activities with Teva Neuroscience, Daiichi Pharmaceutical Corporation, Eli Lilly & Company, Sanofi-Aventis Pharmaceuticals, Inc., PRIME Education, Inc., Projects in Knowledge, Guidepoint Global, Eisai Inc., Biogen Idec, Xenoport, Novartis, Schering-Plough Biopharma, Ono Pharmaceutical, Elan Corporation, Acorda, IMPAX, GlaxoSmithKline, Inc., and EMD Serono. Dr. Vollmer has recieved research support from EMD Serono, Teva Neuroscience, Novartis, Daiichi Pharmaceutical Corporation, Genzyme Corporation, Ono Pharmaceutical, Eli Lilly & Company, Sanofi-Aventis Pharmaceuticals, Inc., IMPAX, and Biogen Idec. Dr. Comi has received personal compensation for activities with Novartis, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Inc., Merck Serono, Bayer Schering, and Biogen Dompe. Dr. Soelberg-Sorensen has received personal compensation for activities with Merck Serono, Biogen Idec, TEVA,Genmab,Elan, Bayer Schering, and Novartis as a speaker and member of the scientific advisory board. Dr. Soelberg-Sorensen has received research support from Biogen Idec, Bayer Schering, Merck Serono, TEVA, Baxter, Sanofi-Aventis, BioMS, Novartis, Bayer, RoFAR, Roche, Genzyme, from the Danish Multiple Sclerosis Society, the Danish Medical Research Council, and the European Union Sixth Framework Programme: Life sciences, Genomics and Biotechnology for health. Dr. Arnold has received personal compensation for activities with Bayer Healthcare, Biogen Idec, Genentech, Inc., NeuroRx Research, Roche Diagnostics Corporation, Schering, Serono, Inc., and Teva Neuroscience. Dr. Arnold Dr. Arnold has received research support from Bayer Healthcare, Biogen Idec, Genentech, Inc., NeuroRx Research, Roche Diagnostics Corporation, Schering, Serono, Inc., and Teva Neuroscience. Dr. Filippi has received personal compensation for activities with ECTRIMS, MSIF, MS Ireland, US NMSS, Bayer-Schering, Biogen-Dompe AG, Genmab, Merck Serono, Pepgen Corporation, Teva, and Sanofi-Aventis. Dr. Filippi has received research support from Teva, Bayer-Schering and Genmab. Dr. Statinov has received research support from Teva Pharmaceuticals. Dr. Kobys has received research support from Teva Pharmaceuticals. Dr. Becker has nothing to disclose. Dr. Jeffery has received personal compensation for activities with Berlex Labortories, GlaxoSmithKline Inc., Pfizer Inc, Serono, Inc. and Teva Neuroscience as a consultant.Dr. Jeffery has received research support from Berlex Labortories, Pfizer Inc, Serono, Inc. and Teva Neuroscience. Dr. Montalban has received personal compensation for activities with Bayer Schering Pharma, Biogen Idec, EMD Merck Serono, Genentech, Genzyme, Novartis, sanofi-aventis, Teva Pharmaceuticals, Almirall and BTG. Dr. Montalban has received research support from Bayer Schering Pharma, Biogen Idec, EMD Merck Serono, Genentech, Genzyme, Novartis, sanofi-aventis, Teva Pharmaceuticals, Almirall and BTG. Dr. Kappos has received research support from Acorda Therapeutics, Actelion, Allozyne, BaroFold, Inc., Bayer Pharmaceuticals Corporation, Bayhill Therapeutics, Biogen Idec, Boehringer Ingelheim Pharmaceuticals, Inc, Elan Corporation, Genmab, GlaxoSmithKline, Inc., Glenmark Pharma, Merck Serono, MediciNova, Novartis, Sanofi-Aventis Pharmaceuticals, Santhera Pharmaceuticals, Shire, Roche Diagnostics, Teva Neuroscience, UCB Pharma, Pfizer Inc, Swiss MS Society, Swiss National Research Foundation, European Union, Gianni Rubatto Foundation, Novartis and Roche Research Foundations. Dr. Boyko has received personal compensation for activities with Novartis, Merck Serono, TEVA, Gensyme, Biogen Idec, Nicomed as a member of advisory boards, a speaker and a participant of clinical trials. Dr. Selmaj has received personal compensation for activities with Genzyme, Ono, and Biogen Idec. Dr. Zipp has nothing to disclose. Dr. Havrodova has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Genzyme Corporation, GlaxoSmithKline, Inc., Novartis, Merck, Sanofi-Aventis Pharmaceuticals, Serono, Inc., and Teva as consultant, speaker and/or advisory board participant. Dr. Cohen has received personal compensation for activities with Biogen Idec, Eli Lilly & Company, Novartis, and Vaccinex. Dr. Cohen has received research support for activities with Biogen Idec, BioMS, Genzyme Corporation, Novartis, Synthon, and Teva Neuroscience.