At the American Academy of Neurology
meeting from April 23 to 27, 2012, there were several interesting presentations. A number of groups reported
results of Phase III trials of new treatments for MS which have been in development for several years. I
will summarize them in the order in which they were presented.
Biogen reported the results of the second Phase III trial
of BG12. The results of the first Phase III study (see ECTRIMS 2011) were quite impressive.
This second trial compared placebo, two different doses of BG12, and glatiramer (Copaxone, one of the current first
line therapies). BG12 decreased the relapse rate by 44% or 51% compared to placebo, depending on dose.
It also had positive effects on disability and disease progression and MRI activity. The side effects
include flushing and gastrointestinal symptoms, worst in the first month of treatment. No serious drug
related side effects were noted. This is an oral agent given 2 or 3 times a day, and it is currently being
reviewed by the FDA.
There were two separate Phase III studies comparing alemtuzumab and Rebif. Alemtuzumab is
a monoclonal antibody which is given in yearly courses. It causes a long-lasting decrease in the numbers
of white blood cells. In one study, the relapse rate on alemtuzumab was 49% lower than on rebif, in the
other, the decrease in relapse rate was 54%. It should be noted that these reductions are compared to rebif,
which itself decreases relapse rate about 32%, so these are very impressive effects. Other measures of
disease activity, such as disability and MRI, were also significantly reduced. This drug has some concerning
side effects, which were known from their previous phase II study. It can cause other autoimmune
diseases, particularly thyroid problems and loss of platelets. There is also an increased rate of serious
is a different monoclonal antibody which blocks the interleukin-2 receptor. This doesn’t kill off
white blood cells, as occurs with alemtuzumab and rituximab, but it has complex effects on immune function. In
this study daclizumab decreased the relapse rate relative to placebo by 51 or 55% depending on dose. It
is given by subcutaneous injection once a month. It was generally well tolerated, but there was one death
from infection and issues with liver toxicity.
We also heard a combined re-analysis of two phase III studies of laquinimod which were reported
at previous meetings. This drug reduces relapse rate by only 21%, which is disappointing. But
it decreased progression of disability by up to 46%. Most of the other treatments we have seem to reduce
relapses more than decreasing disability, so this is an interesting finding. I’m not sure what the
future for this treatment is, since we have an increasing number of effective treatments for MS.
The final notable clinical trial was the
CombiRx trial which compared the combination of Copaxone and Avonex to either drug alone. There was no
placebo group in this study. The relapse rate in this study was very low overall, but there was no clinical
benefit to the combined therapy. The number of relapses and the progression of disability were no better.
Patients on the combination did have decreased activity on MRI. Even though the results are negative,
this study makes an important point for neurologists treating MS. It is tempting to combine different therapies,
but you can’t just assume that it will work.