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`| attended the ECTRIMS meeting October 19-22, 2011 in Amsterdam. This year there
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`B were a number of importantclinical trials, many of which were Phase Ill resultsfrom
`drugs which looked very promising in Phaseil.
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`oe #2 Daclizumab: This is a monoclonal antibodygiven as a once a monthinjection, It bindsthe
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`2 interleukin-2 receptor.
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`It decreased relapse rate by about 50% compared to placebo, and
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`BG12: The most important results were from a Phase Ill study of a drug called BG12, This
`is an oral medication, given either 2 or 3 times a day. They did a 96 week study with over
`me 1200 subjects in 3 groups. The annual relapse rate on placebo was 0.364, while it was
`0.172 on lower dose BG12 and 0.189 on the higher dose of BG12. This is a reduction of 53
`or 48% in the relapse rate. There was also a marked effect on MRI activity, with a
`reduction of about 90% in enhancing lesions and 85% in new T2 lesions. The main side
`ffects were flushing and Gl irritation. These are impressive results, both for efficacy and
`| safety.
`In their Phase Il study (see the report from ECTRIMS 2009}this drug reduced
`relapse rate by 30%, so these results are a little surprising. Asecond phase [ll study is in
`progress, and results should be available soon.
`If they see the same benefits, this will be
`an attractive medicine.
`@ Laquinimod: results of the second phaseIf! trial comparing laquinimod, placebo and
`# Avonex. Laquinimod had a modest effect on numberof relapses, decreasing them by
`fee about 18%. Safety appears good. This agent has the advantage of being oral, but doesn’t
`ee offer any increased effectiveness over available treatments. (see AAN 2011 for other
`@ results with this drug.)
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` @ also decreased disability and MRI activity. There was one death from aninfection, anda
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`: gre WS -O\WOZ
`2
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`hitpv/wonwjwiindseymd.convid77.html
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`Biogen Exhibit 2229
`Mylanv. Biogen
`IPR 2018-01403
`
`16/2019
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`small increase in the rate of serious infections.
`fq Alemtuzumab: This is a monoclonal antibody that depletes a wide range of white blood
`Bi cells. [tis given yearly ina series of infusions over 5 days.
`In this study, they treated
`i a Eres Basic
`a
`recently diagnosed subjects who had not recaived any previous treatment, and compared
`iefelCeCe
`; en TESTS a ;
`the alemtuzumab to Rebif. Alemtuzumab decreased relapse rate by 55% compared to
`FUaig ee
`a Rebif (note this is not compared to placebolike the other trials). It also decreased
`ct ar ReeT x
`disability slightly. Notable side effects included autoimmunethyroid and platelet
`j problemsas seen in previous studies, This lookslike a very effective medicine, but with
`i SE Li aad
`g some concerning side effects. These results are very similar to their phaseII trial reported
`: aSoe Pane
`in 2008, and a second phaseIII study is in progress.
`SearedS
`Atacicept: One puzzling result was a study of atacicept, a protein that interferes with B
`fi cell activity. Depletion of B cells is very effective for MS, so we expected that atacicept
`eeecrc
`would also improve MS. But instead, it seemed to increase disease activity. The
`Me difference in effect between blockingBcell activity and getting rid of B cells completelyis
`enerrad | ee
`fm Unexplained and unexpected. But it reinforces the point that often treatments do not do
`m what we expect they \will, andeverycrus needs rigorous testing before we acceptit as
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`mead effective.
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`een
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`3224 J. William Lindsey, MD
`University of Texas Multiple Sclerosis Research Group
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`Page 1 of 2
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`Biogen Exhibit 2229
`Mylan v. Biogen
`IPR 2018-01403
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`an|Houston, Texas copyright 2007-2020 John Willam Lindsey
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