Window of opportunity in MS treatmentThursday, October 03, 2013, 12:01 - 12:13
TOPIC main outcomes: efficacy and safety of once-daily oral teriflunomide in patients with clinically isolated syndrome A. Miller, J. Wolinsky, L. Kappos, G. Comi, M.S. Freedman, T. Olsson, A. Rugina, D. Bauer, J. Delhay, B. Wamil, P. Truffinet, P. O’Connor (New York, Houston, US; Basel, CH; Milan, IT; Ottawa, CA; Stockholm, SE; Chilly-Mazarin, FR; Bridgewater, US; Toronto, CA)
Introduction: Teriflunomide is a novel, once-daily, oral immunomodulator approved in the USA, Argentina and Australia for treatment of relapsing MS (RMS). Clinical studies of teriflunomide in patients with RMS (TEMSO NCT00134563; TOWER NCT00751881) showed consistent efficacy across key clinical measures and a well-characterised safety profile. TOPIC (NCT00622700) is a phase 3 clinical trial conducted to assess the efficacy and safety of teriflunomide in patients with a first clinical episode suggestive of MS (clinically isolated syndrome, CIS).
Methods: In TOPIC, a double-blind, placebo-controlled, parallel-group study, 618 patients with CIS were enrolled from Feb 2008 to Sep 2012 (planned end Dec 2012) and randomized to placebo, teriflunomide 7 mg or teriflunomide 14 mg. TOPIC ended early as revised diagnostic criteria enabled earlier diagnosis of MS. The primary and key secondary endpoints were conversion to clinically definite MS (CDMS) and occurrence of a new clinical relapse or MRI lesion. Other efficacy endpoints and safety/tolerability were also assessed.
Results: Baseline characteristics were generally well balanced among treatment groups. Of the randomized population (n=618), 59.1% had monofocal and 40.9% had multifocal lesion presentation, and 31.4% had >=1 Gd-enhancing lesion. Median time since first neurological event was 2 months. Compared with placebo, teriflunomide 14 mg reduced the risk of conversion to CDMS by 42.6% (p=0.0087), with a probability of conversion to CDMS at 108 weeks of 24.0% (probability for placebo group 35.9%). Teriflunomide 14 mg also reduced the risk of occurrence of new relapse or new MRI lesion by 34.9% (p=0.0003). Teriflunomide 7 mg reduced the risk of conversion to CDMS by 37.2% (p=0.0271; 108-week probability 27.6%), and the risk of occurrence of new relapse or new MRI lesion by 31.4% (p=0.0020). The proportion of patients experiencing adverse events (AEs) was similar across treatment groups. The most common AEs reported more frequently in the teriflunomide arms included alanine aminotransferase elevation, headache, hair thinning (14 mg only), diarrhoea and paraesthesia.
Conclusions: Results from the TOPIC study demonstrate the efficacy of teriflunomide 14 mg and 7 mg in the treatment of patients with CIS, highlighting the ability of early intervention with teriflunomide to delay onset of MS symptoms. To date, all teriflunomide phase 3 studies have shown consistent safety and efficacy, and greater efficacy for a 14 mg dose.
Study supported by Genzyme, a Sanofi company.
Aaron E Miller has received research support from Acorda Therapeutics, Biogen Idec, Genentech, Genzyme Corporation, sanofi-aventis, Novartis, Osmotica, Roche and Teva. He has received consulting fees from Acorda Therapeutics, , Biogen Idec, , EMD Serono, GlaxoSmithKline, Merck Serono, Novartis, Nuron Biotech, ONO and sanofi-aventis.
Jerry S Wolinsky has received consulting/speaker fees from Celgene, Consortium of MS Clinics, Genzyme, Janssen RND, Hoffman LaRoche, Medscape CME, Novartis, PRIME, sanofi-aventis, Serono Symposia International Foundation, Teva, Teva Neurosciences; royalties from Millipore (Chemicon International) Corporation; research / contractual support from: Genzyme, National MS Society, National Institutes of Health, and sanofi
Ludwig Kappos has received research support from Actelion, Advancell, Allozyne, BaroFold, Bayer Health Care Pharmaceuticals, Bayer Schering Pharma, Bayhill, Biogen Idec, BioMarin, CSL Behring, Elan, Genmab, Genmark, GeNeuro SA, GlaxoSmithKline, Lilly, Merck Serono, MediciNova, Novartis, Novonordisk, Peptimmune, sanofi-aventis, Santhera, Roche, Teva, UCB, and Wyeth, and from the Swiss MS Society, the Swiss National Research Foundation, the European Union, and the Gianni Rubatto, Novartis, and Roche Research Foundations.
Giancarlo Comi has received consulting fees from Novartis, Teva Pharmaceutical Ind. Ltd, sanofi-aventis, Merck Serono, Actelion and Bayer Scherin; lecture fees: Novartis, Teva Pharmaceutical Ind. Ltd, sanofi-aventis, Merck Serono, Biogen Dompè, Bayer Schering, and Serono Symposia International Foundation.
Mark S Freedman has received research and educational grant support from Bayer Healthcare and Genzyme; honoraria/consultation fees from Bayer Healthcare, Biogen Idec, EMD Canada, Novartis, sanofi-aventis, Teva Canada Innovation and is a member of Company Advisory Board/Board of Directors/or other similar group for Bayer Healthcare, Biogen Idec, Merck Serono, Novartis, sanofi-aventis, and Celgene.
Tomas P Olsson has received consulting fees and/or research support from Biogen Idec, Merck Serono, and sanofi-aventis; participation in scientific advisory boards and/or speaking activities: Merck Serono, Biogen Idec and sanofi-aventis.
Anca Rugina, Deborah Bauer, Jean-Luc Delhay, Barbara D. Wamil, and Philippe Truffinet are employees of Sanofi
Paul O’Connor has received consulting fees and/or research support from Actelion, Bayer, Biogen Idec, BioMS, Cognosci, Daiichi Sankyo, EMD Serono, Genentech, Genmab, Novartis, Roche, sanofi-aventis, and Teva.