Emerging Therapies in Multiple Sclerosis
The field of multiple sclerosis (MS) therapeutics, particularly for relapsing-remitting MS (RRMS), is rapidly evolving. Many agents are currently in various stages of clinical trials, with several medications presently under regulatory review. New treatme
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1 Introduction The field of multiple sclerosis (MS) therapeutics, particularly for relapsing-remitting MS (RRMS), is rapidly evolving. Many agents are currently in various stages of clinical trials, with several medications presently under regulatory review. New treatments for MS pose exciting opportunities for disease control of relapsing MS; however, new mechanisms of action carry the potential for new side effects, novel adverse events, and the need for vigilant monitoring to ensure their safe and effective use. This chapter will review several promising emerging MS therapies, with an emphasis on two agents that have completed Phase III studies (daclizumab and ocrelizumab), as well as new approaches of great interest to patients with MS: remyelination therapy and the potential use of stem cells.
S. Klineova (*) • S. Krieger Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, NY, USA e-mail: [email protected] A. Miller (ed.), Handbook of Relapsing-Remitting Multiple Sclerosis, DOI 10.1007/978-3-319-40628-2_5, © Springer International Publishing Switzerland 2017
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S. Klineova and S. Krieger
5.2 New Monoclonal Antibodies Several new monoclonal antibodies are currently in the developmental pipeline for relapsing MS (Table 5.1). This chapter will review two of them, daclizumab and ocrelizumab, in further detail.
5.2.1 Daclizumab Daclizumab, a humanized monoclonal antibody (Ab) targeting the CD25 subunit of the interleukin (IL)-2 receptor, is currently approved by the FDA for use in rheumatoid arthritis and other autoimmune diseases. Initially thought to decrease T-cell expansion via a reduction in IL-2 signaling, daclizumab was subsequently found to increase the levels of circulating CD56bright natural killer (NK) cells. The contact dependent inhibitory effect of NK cells on T-cell survival is the proposed mechanism of action in relapsing MS [1]. It has been studied as a once-monthly subcutaneous injection. After a successful Phase II study (SELECT) [2] and its 1 year extension (SELECTION) [3], the efficacy of daclizumab (monthly 150 mg subcutaneous injection) in RRMS was further assessed in a Phase III, randomized, multicenter, double- blind study, using the weekly intramuscular interferon (IFN) β-1a as an active comparator (DECIDE trial). The DECIDE trial enrolled over 1800 patients and successfully met its primary outcome by demonstrating a 45 % annualized relapse rate (ARR) reduction compared to weekly IFN β-1a (P 99 % reduction in total T1 Gd + lesions
1. Phase II trial 600 mg and 2000 mg 89 % and 96 % reduction in total T1 Gd + lesions ARR reduction 80 and 73 % 2. OPERA I and II Phase III: ARR reduction 46 % vs. interferon, 95 % reduction in T1 Gd + lesions
1. HERMES Phase II RRMS 91 % reduction in total T1 Gd + lesions 2. OLYMPUS Phase II/III PPMS Delayed time to CDP in younger individuals
1. SELECT Phase II 2. SELECTION Phase II extension 3. DECIDE Phase III ARR reduction 45 %
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