The NEW ENGLAND IOURNAL ofMEDlClNE
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`ORIGINAL ARTICLE
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`1
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`B-Cell Depletion with Rituximab in
`Relapsing—Remitting Multiple Sclerosis
`
`Stephen L. Hauser, M.D., Emmanuelle Waubant, MD, Ph.D,,
`Douglas L. Arnold, MD, Timothy Vollmer. M.D.,jacl< Antel, MD,
`Robert]. Fox, M,D., Amit Bar-Or, MD. Michael Panzara. M.D.,
`Neena Sarkar. Ph.D., Sunil Agarwal. M.D..Annette LangereGould, MD, PhD,
`and Craig H. Smith, M.D., for the HERMES Trial Group"?
`ABSTRACT
`
`DACKG IOU N D
`
`There is increasing evidence that B lymphocytes are involved in the pathogenesis of
`multiple sclerosis, and they may be a therapeutic target. Rituximab, a monoclonal
`antibody, selectively targets and depletes CD20+ B lymphocytes.
`METHODS
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`In a phase 2, double-blind, 48-week trial involving 104 patients with relapsing—remit»
`ting multiple sclerosis, we assigned 69 patients to receive 1000 mg of intravenous
`rituximab and 35 patients to receive placebo on days 1 and 15. The primary end point
`was the total count ofgadolinium—enhancing lesions detected on magnetic resonance
`imaging scans of the brain at weeks 12, 16, 20, and 24. Clinical outcomes included
`safety, the proportion of patients who had relapses, and the annualized rate of re—
`lapse.
`
`nesuus
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`As compared with patients who received placebo, patients who received rituximab
`had reduced counts of total gadoliniumcnhancing lesions at weeks 12, 16, 20, and
`24 (P<0.001) and of total new gadolinium—enhancing lesions over the same period
`(P<0.001); these results were sustained for 48 weeks (P<0,001). As compared with
`patients in the placebo group, the proportion of patients in the rituximab group
`with relapses was significantly reduced at week 24 (14.5% vs. 34.3%, P2002) and
`week 48 (20.3% vs. 40.0%, P=0.04). More patients in the rituximab group than in the
`placebo group had adverse events within 24 hours after the first infusion, most of
`which were mild—to-moderate events; after the second infusion, the numbers of
`events were similar in the two groups.
`CONCLUSIONS
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`A single course of rituximab reduced inflammatory brain lesions and clinical re-
`lapses for 48 weeks. This trial was not designed to assess long-term safety or to
`detect uncommon adverse events. The data provide evidence of B-cell involvement
`in the pathophysiology of relapsing—remitting multiple sclerosis. (ClinicalTrialS.g0v
`number, NCTOOO97188.)
`
`From the Department of Neurology, Uni-
`versity otCalit’ornia at San Francisco, San
`Francisco (S.L.H., E.W.]; Montreal Neu-
`rological
`Institute, McCall University
`[D,L.A., j.A., A.B,~O,), and NeuroRx Re-
`search (D.L.A.) —both in Montreal: Bar»
`row Neurology Clinics, Phoenix, AZ (TM);
`Mellen Center for Multiple Sclerosis, Cleve-
`land Clinic, Cleveland (R.J.F.); Biogen
`idec, Cambridge, MA (MR); and Genenv
`tech, South San Francnsco. CA (N.S..
`S.A., A.L.-G., C.H.Si), Address reprint re-
`quests to Dr. Hauser at the Department
`of Neurology. University of California at
`San Francisco, 505 Parnassus Ave., Box
`0114, San Francisco, CA 94143-0114, or at
`hausers®neurologyucsfiedu.
`
`*Other investigators who participated in
`the Helping to Evaluate Rituxan in Re-
`lapsing-Remitting Multiple Sclerosis
`(HERMES) Trial Group are listed in the
`Appendix.
`
`N Englj Med 2008;353:676-83.
`Copyright © 2003 Massachusetts Medical Sonny,
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`676
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` N ENGLJ MED 358,7 www.mmonc
`
`reenuanv 14, 2008
`The New England Journal of Medicine
`Downloaded from nejmmg on February 5. 2015. For personal use only. No other uses without permission.
`Copyright © 2008 Massachusetts Medical Society. All rights reserved.
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`Biogen Exhibit 2226
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