Teriflunomide

14 mg dose was associated with a 36.3% reduction in ARR (0.319 versus 0.501 for placebo) and a 31.5% reduction in the risk of 12-week sustained accumulation of disability (as measured by the Expanded Disability Status Scale), whereas the 7 mg dose was associated with a 22.3% reduction in ARR (0.389) but did not affect the risk of 12-week sustained accumulation of disability

(19)

Genzyme reports positive top-line results of TOWER, a pivotal phase III trial for AUBAGIO(TM*) (teriflunomide) in relapsing multiple sclerosis

Genzyme, 1 Jun 2012

Accessed on 4 Jun 2012 from http://www.businesswire.com/news/genzyme/20120531006926/en.

(24)

Genzyme presents second Phase III study of once-daily oral AUBAGIO® (teriflunomide) confirming significant impact on disability

Genzyme, 12 Oct 2012

Accessed on 16 Oct 2012 from http://www.businesswire.com/news/genzyme/20121012005423/en.

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Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial.

Confavreux C, O'Connor P, Comi G, Freedman MS, Miller AE, Olsson TP, Wolinsky JS, Bagulho T, Delhay J-L, Dukovic D, et al.

Lancet Neurol. 2014 Jan 22. Epub 1969 Dec 31. PMID: 24461574. Abstract

; post hoc analysis to evaluate the effects of teriflunomide on severe relapses showed that the drug had positive effects [for example, the 14 mg dose reduced the annualized rate of (i) relapses with sequelae (defined by an increase in the Expanded Disability Status Scale) by 36.6%, (ii) relapses with sequelae (defined by the investigator) by 53.5%, and (iii) relapses resulting in hospitalization by 33.6%], suggesting that teriflunomide may reduce relapse-associated healthcare costs

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Teriflunomide reduces relapses with sequelae and relapses leading to hospitalizations: results from the TOWER study.

Miller AE, Macdonell R, Comi G, Freedman MS, Kappos L, Mäurer M, Olsson TP, Wolinsky JS, Bozzi S, Dive-Pouletty C, et al.

J Neurol. 2014 Jun 28. Epub 2014 Jun 28. PMID: 24972678. Abstract

Teriflunomide reduced the annualized relapse rate by 31% (at either dose), disability progression (at 14 mg dose), and lesion load (assayed by MRI) relative to placebo

(6)

Development of oral immunomodulatory agents in the management of multiple sclerosis.

Nicholas R, Giannetti P, Alsanousi A, Friede T, Muraro PA

Drug Des Devel Ther. 2011; 5:255-74. Epub 2011 May 10. PMID: 21625416. Abstract

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Randomized trial of oral teriflunomide for relapsing multiple sclerosis.

O'Connor P, Wolinsky JS, Confavreux C, Comi G, Kappos L, Olsson TP, Benzerdjeb H, Truffinet P, Wang L, Miller A, et al.

N Engl J Med. 2011 Oct 6; 365(14):1293-303. PMID: 21991951. Abstract

; additional analysis showed that the positive effects of the drug were consistent across a variety of patient subgroups

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Pre-specified subgroup analyses of a placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis.

Miller AE, O'Connor P, Wolinsky JS, Confavreux C, Kappos L, Olsson TP, Truffinet P, Wang L, D'Castro L, Comi G, et al.

Mult Scler. 2012 Jun 21. Epub 1969 Dec 31. PMID: 22723573. Abstract

; 14 mg and 7 mg doses were associated with 67.4% and 39.4% lower increases in total lesion volume as compared to placebo

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Magnetic resonance imaging outcomes from a phase III trial of teriflunomide.

Wolinsky JS, Narayana PA, Nelson F, Datta S, O'Connor P, Confavreux C, Comi G, Kappos L, Olsson TP, Truffinet P, et al.

Mult Scler. 2013 Feb 27. PMID: 23447359. Abstract

; posthoc analysis showed that the 7 mg and 14 mg doses reduced the annualized rate of relapses with neurological sequelae by 32% and 36%, respectively, the relapses that led to hospitalization by 36% and 59%, and relapses that required steroid treatment by 29% and 34%, suggesting that the drug's effects might result in lower healthcare expenses

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Teriflunomide reduces relapse-related neurological sequelae, hospitalizations and steroid use.

O'Connor PW, Lublin FD, Wolinsky JS, Confavreux C, Comi G, Freedman MS, Olsson TP, Miller AE, Dive-Pouletty C, Bégo-Le-Bagousse G, et al.

J Neurol. 2013 Jul 14. Epub 2013 Jul 14. PMID: 23852658. Abstract

; individuals who completed this study were given the option to participate in an extension study with a total duration about about 6 years (from the time the first patient enrolled), to continue receiving 7 mg or 14 mg drug or, if received placebo, to be randomized to receive 7 mg or 14 mg

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Long term safety and efficacy study of teriflunomide 7 mg or 14 mg in patients with relapsing-remitting multiple sclerosis

ClinicalTrials.gov, 31 Mar 2011

Accessed on 5 Jan 2012 from http://clinicaltrials.gov/ct2/show/NCT00803049.

; additional analysis indicated that teriflunomide slows brain atrophy, such that at month 12, the median percent reduction in brain volume was 0.39 (14 mg dose) or 0.40 (7 mg dose) versus 0.61 (placebo) and at month 24, the reduction was 0.90 (14 mg dose) or 0.94 (7 mg dose) versus 1.29 (placebo) (meeting report, 2015)

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New Analysis Suggests Aubagio® (teriflunomide) Slows Brain Atrophy in People with Relapsing Multiple Sclerosis

Genzyme, 7 Oct 2015

Accessed on 13 Oct 2015 from http://news.genzyme.com/press-release/new-analysis-suggests-aubagio-teriflunomide-slows-brain-atrophy-people-relapsing-multi.