Previously unpublished results of clinical trials of Lemtrada (alemtuzumab) appears to contain key information as to why many multiple sclerosis patients who use it develop other autoimmune diseases.
Researchers looked at the immune cell mix after Lemtrada depleted many of those cells. They discovered that certain B-cells repopulate the body earlier than key regulatory T-cells, leading to an imbalanced immune system that is prone to turn on itself.
Although the findings pertained specifically to Lemtrada, they suggest that naturally occurring immune cell imbalance could lead to autoimmune diseases, researchers said.
The insight opens the door to scientists developing ways to counter the imbalance to protect MS patients from additional diseases
A key lesson from the study was the importance of fully analyzing and publishing clinical-trial information.
The research, “Interpreting Lymphocyte Reconstitution Data From the Pivotal Phase 3 Trials of Alemtuzumab,” was published in the journal JAMA Neurology.
Researchers from Queen Mary University of London used a Freedom of Information request to the European Medicines Agency to obtain full results of the Phase 3 clinical trials of Lemtrada.
Scientists know that many people who take Lemtrada develop autoimmune diseases. Those who conducted the trials had presented some of the unpublished information at conferences, but had yet to submit studies involving those results to scientific journals.
“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were very surprised to find such important information on B-cell dynamics were only partially described and remained unpublished, even though they were observed and analysed several years ago following the pivotal Phase 3 trials,” Klaus Schmierer, the senior author of the study, said in a press release.
When the Queen Mary research team looked at the unpublished information, they realized that the key to why patients become vulnerable to autoimmune disease was right there.
Lemtrada, a very effective MS treatment, targets a molecule called CD52 that is in both T-cells and B-cells. When patients begin the treatment, it nearly eliminates both cell types. As time goes on, T-cell counts remain low, but B-cells rebound.
T-cells usually keep B-cells in check. With few T-cells, B-cells are able to proliferate, leading to an imbalance between the cell types.
In addition, an abundance of B-cells contributes to the production of antibodies against Lemtrada, potentially rendering the drug useless with prolonged use.
The unpublished information also provided another crucial insight. Although most types of B-cells increased after treatment, even reaching numbers higher than before Lemtrada was administered, the number of memory B-cells remained low. The researchers believe this could have contributed to Lemtrada’s effectiveness against MS.
“Interrogating the original data from a different perspective opened our minds to alternative explanations,” Schmierer said. “This made us discard the science dogma that we think is leading people to look in the wrong place for solutions.”
Although “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,” he contended.
In an editorial expressing gratitude to the Queen Mary team, Dr. Lawrence Steinman of Stanford University noted that studying a therapy’s side effects also offers an excellent opportunity to better understand the disease and its treatments.
Rectifying the immune-cell imbalance that Lemtrada triggers may limit the risk of another autoimmune disease developing, researchers said. That could make Lemtrada an even better therapy option.
“This new information will help contribute to the effective management of people with MS, firstly during the decision process about disease modifying treatment, and secondly in people who have been treated with Alemtuzumab [another MS therapy], to ensure the risks associated with dangerous side effects are minimized,” Schmierer said.
He underscored that the study did not provide all the answers, however.
“There remain some unanswered questions, based on what we saw,” he said. “This shows us why it is important for total transparency and total access to all anonymous trial data.”