Alemtuzumab treats relapsing forms of multiple sclerosis, but is accompanied with a 50% risk of secondary autoimmune diseases.
Through a Freedom of Information Act request, scientists from Queen Mary University of London (QMUL) gained access to datasets from the phase 3 trial of alemtuzumab (Lemtrada).
The FDA approved alemtuzumab as a disease-modifying therapy for patients with relapsing forms of multiple sclerosis (MS). It is approved in more than 60 countries and used by more than 12,000 patients worldwide.
But due to serious risks of autoimmune conditions, infusion reactions, and malignancies, alemtuzumab received a boxed warning and is now only available through a US restricted program called Lemtrada Risk Evaluation and Mitigation Strategy (REMS). The risk of developing secondary autoimmune diseases is nearly 50%.
“The use of alemtuzumab should generally be reserved for patients who have had an inadequate response to 2 or more drugs indicated for the treatment of MS,” the FDA wrote.
After receiving the data from the European Medicines Agency, the scientists analyzed and interpreted the results. Published in JAMA Neurology, the study showed a significant and rapid repopulation of a subset of B cells in the absence of successful cell regulation.
However, controlling this “B cell subset overshoot” after alemtuzumab is administrated, and until T cell regulation recovers, might reduce the risk of secondary autoimmune diseases and improve the medication.
Another finding was the loss of memory B cells, which could offer a new explanation for why alemtuzumab is effective in patients with MS, according to the authors.
“We were very surprised to find such important information on B cell dynamics were only partially described and remained unpublished, even though they were observed and analyzed several years ago following the pivotal phase 3 trials,” said lead author Dr Klaus Schmierer. “Interrogating the original data from a different perspective opened our minds to alternative explanations. This made us discard the science dogma that we think is leading people to look in the wrong place for solutions.
“There remain some unanswered questions, based on what we saw. This shows us why it is important for total transparency and total access to all anonymous trial data. Whilst we appreciate release of data is part of the drug-marketing process, it is in the public interest that all information collected is made unconditionally available, within a reasonable time frame.”