The most important results were from a Phase III 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 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 effects were
flushing and GI irritation. These are impressive results, both for efficacy and safety. In
their Phase II study (see the report from ECTRIMS 2009) this drug reduced relapse rate by 30%, so these results are a little
surprising. A second phase III 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 phase III 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 results with this drug.)
This is a monoclonal antibody given as a once a month injection. It binds the interleukin-2 receptor.
It decreased relapse rate by about 50% compared to placebo, and also decreased disability and MRI activity.
There was one death from an infection, and a small increase in the rate of serious infections.
This is a monoclonal antibody that depletes a wide range of white blood 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 Rebif (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 some concerning side effects.
These results are very similar to their phase II trial reported in 2008, and a second phase III study is in progress.
One puzzling result was a study of atacicept, a protein that interferes with B 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 difference in effect between 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 what we expect they will, and every drug needs rigorous testing before we accept it as effective.