February 17, 2011
By Staff Reporter
The decision came in the wake of the discovery that one patient who had been taking the drug had died from an extremely rare disease of the brain and spinal cord. A second case of the disease, which was suspected at the time Elan made its announcement, has subsequently been confirmed, though the patient is still alive.
Executives in Elan and the company that partners it on the drug, Biogen, have emphasized that a link has not been proven between Tysabri and the disease, progressive multiphocal leukencephalopathy. However, the circumstantial evidence is disturbing — the two people who contracted PML were part of a pool of just 500 people who had been involved in clinical trials of the drug over two years, while PML’s incidence in the general population is no greater than 1 in 100,000.
Now, the FDA’s decision to approve the drug three months ago is coming under scrutiny. Attention has also begun to focus on why the warnings of a Stanford University professor about the alleged dangers of the drug were not heeded.
The specifics of the science behind a drug like Tysabri are dizzyingly complex. The basic principles, however, are not.
In multiple sclerosis, the body’s immune system goes wrong. So-called T-cells, which under normal circumstances fight off infections, attack a healthy substance called myelin that covers nerve endings. In doing so, they severely impair the functioning of the entire nervous system, bringing on symptoms that range from numbness of limbs to paralysis and, in a small number of cases, dementia.
The idea behind Tysabri was simple: stop the errant T-cells from doing their damage. The risk, however, was also clear: if the “bad” T-cells were blocked, would their healthy counterparts, so vital for rebuffing other ailments, also be impeded?
Up until last month, the answer to that question seemed to be no. Clinical trials showed Tysabri reduced M.S. episodes by 66 percent, and there appeared to be no serious side effects. But the confidence engendered by those results has evaporated.
If Tysabri does not have a detrimental effect on the immune system, skeptics ask, why have two patients been stricken with PML, a disease almost exclusively seen in those with compromised immunity, especially people in the late stages of AIDS?
The crisis over Tysabri is all the more discomfiting because of the doubts about the drug that had already been expressed. In 1992, Professor Lawrence Steinman of Stanford University was among the team that discovered the compound that seemed to block aberrant T-cells. But Steinman also came to fear the possible repercussions for the immune system as a whole.
“You don’t want to stop movement everywhere,” Steinman told the Boston Globe last week. “An army unable to respond to threats is not good. To me, it was a no-brainer that there was a risk of opportunistic infections.”
Steinman raised these concerns frequently, but they appear to have been disregarded — possibly because the Stanford academic has a stake in two companies developing their own M.S. drugs.
Steinman did not respond to a request for an interview for this article.
The way in which Tysabri was approved is also the subject of heated debate. The FDA has introduced a number of measures in recent years geared toward speeding up the process by which drugs become available to the general public.
The policy has honorable origins. It came partly in response to complaints by AIDS campaigners in the late 1980s that the regulatory body’s procedures were delaying potentially life-saving treatments. Now, however, people see cases like Tysabri’s as evidence that new drugs are not being sufficiently scrutinized.
“There is an understandable desire to get these drugs out to people quickly, especially when those people have a chronic, life-threatening illness,” Arthur Levin of the New York-based Center for Medical Consumers said. “But the question is whether it does a disservice to the public by putting them on the market before we have found out all we need to know.”
Levin draws attention to the fact that, since 1992, drug companies have paid so-called “user fees” to the FDA in return for the regulatory body agreeing to decide more rapidly whether their products will be approved. Critics like Levin argue that there is, at the very least, a potential conflict of interest in the FDA sitting in judgment upon products made by companies that pay it money.
“The concern would be that the situation is one in which we do not let science dictate approval, but rather let it be dictated by some kind of artificial management goal,” he said.
Even Levin acknowledged, however, that it is impossible to strike a perfect balance between caution and expeditious approval.
“You can never get it right, because you can never know enough,” he said.