A new study of patients who received a promising anti-inflammatory drug found no new cases of a serious brain infection linked to the drug in large clinical trials halted in early 2005.
Scientists completed a study of more than 3,000 patients who received natalizumab, the anti-inflammatory drug. The study found no new cases of progressive multifocal leukoencephalopathy (PML) and confirmed the three previously identified cases of PML associated with use of the drug.
One fatal and one nonfatal case of PML occurred in a trial using natalizumab as a multiple sclerosis treatment; a second fatality happened in a trial that used the drug to treat patients with Crohn’s disease, an inflammatory bowel disorder.
“Our analysis suggests about one in every 1,000 people who took natalizumab contracted this disease; however, there weren’t enough patients exposed to the drug to allow us to precisely estimate the risk, which could be as low as one in 5,000 or as high as one in 300,” said senior author David B. Clifford, M.D., the Melba and Forest Seay Professor of Clinical Neuropharmacology in Neurology at the School of Medicine.
The results of the study, along with two separate studies of natalizumab’s effectiveness as an MS treatment, are published in the March 2 New England Journal of Medicine.
The study played a key role in Food and Drug Administration (FDA) hearings this week that led an FDA advisory panel to recommend the FDA restore U.S. access to the drug.
The brand name of natalizumab, jointly developed by Biogen Idec and Elan Corp., is Tysabri. The drug is a monoclonal antibody that binds to inflammatory immune T cells and prevents them from crossing membranes that protect the brain and the central nervous system.
Prior to the studies that were halted last year, studies showed a 66 percent reduction in the rate of relapses in MS patients treated with the natalizumab, which has to be injected monthly.
“Patients with MS are eager to access more effective therapy,” he said. “But regulators, physicians and patients alike will first have to weigh the risks of a potentially fatal brain infection against the benefits that this drug may afford.”
The links between natalizumab and PML onset are still unclear, but based on their prior dealings with the disorder, PML experts such as Clifford strongly suspect an immune system connection.
“As many as half of all adults are infected with the virus that causes PML, which normally doesn’t bother us,” he said. “It only becomes a problem in those with suppressed immune systems, where it can enter the brain and cause PML. That includes AIDS patients, organ-transplant patients and patients with blood-related malignancies such as leukemia. And even in those patients it’s still rare — we’ve seen about 50 cases over the last decade at the School of Medicine.”
Clifford said the concerns researchers are now confronting in natalizumab will likely have to be considered again as other drugs are developed using the same customized targeting techniques.
“This drug is a good example of the potential of developing drugs with very specific biological targets in mind,” Clifford said. “But this experience also reminds us that there are a lot of hidden icebergs in the ocean we’re navigating, and we’re going to bump up against those icebergs and have to work out ways to navigate around them.”