Lessons for clinical trials from natalizumab in multiple sclerosis

Concerns over the fast tracking of new drugs for commercial licensing are raised by a senior doctor in this week's British Medical Journal.

It follows approval of natalizumab, a new drug for multiple sclerosis, and its recall three months later, after three trial patients developed a life threatening condition while being treated.

Natalizumab was licensed by the US Food and Drug Administration in 2004 for use in relapsing multiple sclerosis on the basis of short term results from two unpublished trials. The FDA granted approval before final trial and cumulative safety data were available. Natalizumab was predicted to be the leading drug for multiple sclerosis, with estimated annual sales in excess of $2bn.

Around 3000 patients took part in the trials and nearly 5000 patients have been treated in the United States since it became commercially available. In the United Kingdom, natalizumab was due for appraisal by the National Institute for Health and Clinical Excellence in 2006.

But on 28 February 2005, natalizumab was recalled after three trial patients developed progressive multifocal leucoencephalopathy (PML), a rapidly progressive neurodegenerative disease. Two of the patients died.

The approval of natalizumab and its recall after three months raises questions about the fast tracking of new drugs by the FDA for commercial licensing, says the author, consultant neurologist Abhijit Chaudhuri. It also highlights the potential risks for patients in trials of new drugs where knowledge of long term efficacy, outcome measures, and safety is lacking.

Short term solutions for a chronic disease like multiple sclerosis are not likely to be effective, and experience with natalizumab should be taken as a signal to change the way we treat this disease, he concludes.