Satellite Symposium -- Researching the Potential for a New
Treatment Paradigm: Alemtuzumab in MS (Sponsored by Bayer HealthCare and Genzyme) *** (Hollie)
At last year's ECTRIMS, there was a lot of exciting data about
alemtuzumab (Campath). Phase 3 studies are now underway so this was
more of an interim update to keep us all interested in the drug.
Mechanism of action (Joanne Jones)
Dr. Jones presented some research on the effects alemtuzumab may have
at a cellular level. The drug depletes both T and B cells; the B
cells that return are mostly naive cells and the T cells are mostly
memory/regulatory cells. Past studies have shown that disability
continues to improve up to three years after treatment ends,
suggesting that the cells that come back secrete neurotrophic
factors. So a series of experiments was conducted to see how cells
behave after exposure to the drug.
One experiment found that T cells (but not B cells or monocytes)
exposed to alemtuzumab increased their production of BDNF
(brain-derived neurotrophic factor) and decreased their production of
IGF-1 (insulin-like growth factor 1). Another experiment exposed
cultured rat embryo neurons to factors secreted by cells exposed to
alemtuzumab and found that neuronal survival was enhanced. (Survival
decreased when the neurons were exposed to cells obtained during
relapses.) A similar experiment found that OPC survival and
maturation was also enhanced by factors secreted by
alemtuzumab-cultured cells.
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The other two talks, given by Krzysztof Selmaj and Edward Fox,
rehashed previous trial data and presented an overview of current
trials. An important bit of good news is that no new cases of ITP
(idiopathic thrombocytopenic purpura) have been reported in the
ongoing trials.
Alemtuzumab significantly increases the proportion of clinically
disease-free patients with RRMS compared to subcutaneous IFN-beta 1a;
results from a phase 2 study (Krzysztof Selmaj)
This data comes from the CAMMS223 study. Compared with IFN-b,
alemtuzumab reduced cumulative relapses over 36 months by 74% and time to sustained accumulation of disease by 71%. EDSS scores decreased on average by 0.39 points in the alemtuzumab arm vs. increasing by 0.38 points in the IFN-b arm. (I think this data has been presented already but I am reporting it here too just in case.)
Dr. Selmaj then presented new data showing that 80% of alemtuzumab
subjects remained relapse-free at 36 months vs. 50% of IFN-b subjects.
Percentages of subjects free from sustained accumulation of disability
were 86% vs. 67%, respectively. (Disability had to be sustained for 3
months to be counted.)