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`i attended the ECTRIMS meeting October 19-22, 2011 in Amsterdam. This year there
`were a number of important clinical trials, many of which were Phase iii results from
`drugs which looked very promising in Phase ii.
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`BG12: The most important results were from a Phase III study of a drug called 3612. This
`is an oral medication, given either 2 or 3 times a day. They did a 96 week study with over
`" .. 1200 subjects in 3 groups. The annual relapse rate on placebo was 0.364, while it was
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`0.172 on lower close 8612 and 0.189 on the higher dose of 8612. This is a reduction of 53
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`or 48% in the relapse rate. There was also a marked effect on MRl activity, with a
`red uction of about 90% in enhancing lesions and 85% in new T2 lesions. The main side
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`ffects were flushing and GI irritation. These are impressive results, both for efficacy and
`, safety.
`in their Phase ll study (see the report from ECTRlMS 2009) this drug red uoed
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`relapse rate by 30%, so these results are a little surprising. A second phase ill study is in
`.3 progress, and results should be available soon.
`If they see the same benefits, this will be
`an attractive medicine.
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`1: Laquinimod: results of the second phase lli trial comparing laquinimod, placebo and
`__ Avonex. Laquinimod had a modest effect on number of relapses, decreasing them by
`about 18%. Safety appears good. This agent has the advantage of being oral, but doesn’t
`-- offer any increased effectiveness over available treatments. (see AAN 2011 for other
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`results with this drug.)
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`.- Daclizumab: This is a monoclonal antibody given as a once a month injection.
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`it binds the
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`It decreased relapse rate by about 50% compared to placebo, and
`interleukin-2 receptor.
`i also decreased disability and MRI activity. There was one death from an infection, and a
`small increase in the rate of serious infections.
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`'- AboutDr. L ds'ey
`Research Interests
`inapiDi-rections
`I _:_I_Links
`Clinic information
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`" Icons-Souls
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`some concerning side effects. These results are very similar to their phase II trial reported
`in 2008, and a second phase lll study is in progress.
`Atacicept: One puzzling result was a study of atacicept, a protein that interferes with B
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`cell activity. Depletion of B cells is very effective for MS, so we expected that atacicept
`would also improve MS. But instead, it seemed to increase disease activity. The
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`. difference in effect betwaen blocking B cell activity and getting rid of B cells completely is
`unexplained and unexpected. But it reinforces the point that often treatments do not do
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`what we expect they will, and every drug needs rigorous testing before we accept it as
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`If; QTPQ m9? 'Oxuo’é
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`J. William Lindsey, MD
`University of Texas Multiple Sclerosis Research Group
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`. Alemtuzumab: This is a monoclonal antibody that depletes a wide range of white blood
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`- cells. It is given yearly in a series of infusions over 5 days.
`in this study, they treated
`recently diagnosed subjects who had not received any previous treatment, and compared
`the alemtuzumab to Rebif. Alemtuzumab decreased relapse rate by 55% compared to
`Rebii’ (note this is not compared to placebo like the other trials). It also decreased
`_. disability slightly. Notable side effects included autoimmune thyroid and platelet
`' problems as seen in previous studies. This looks like a Very effective medicine, but with
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`Biogen Exhibit 2229
`Mylan v. Biogen
`IPR 2018-01403
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`::_ Houston. Texas
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`copyright 2007-2020 John William Lindsey
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