Two new cases of progressive multifocal leukoencephalopathy (PML) in patients treated with Tysabri (natalizumab) reported in July have increased uncertainty over the multiple sclerosis drug's prospects. Few, however, believe Tysabri will be pulled from the market as it was in February 2005 when three people developed the rare, viral-induced disease (Nat. Biotechnol. 23, 397–398, 2005). In 2006, Tysabri returned to the US market and was approved for use in the EU (Nat. Biotechnol. 24, 874, 2006) under controlled access plans designed to promote early detection of PML. Though touted as a potential blockbuster, the renewed safety concerns mean Tysabri may not achieve the commercial success hoped for by Cambridge, Massachusetts–based Biogen Idec and its marketing partner Elan of Dublin. The two latest patients to develop PML—both in the EU—were using Tysabri alone, in contrast to earlier cases seen in combination trials of Tysabri with Avonex (interferon β-1a). “This is a little bit of a splash of cold water in the face,” says Clyde Markowitz, director of the Multiple Sclerosis Center at the University of Pennsylvania, Philadelphia. “A lot of people felt that the combination of therapies may have been responsible.” August brought Biogen more bad news, when a federal judge refused to transfer a lawsuit over a patient's death from a Boston court to a federal court in Iowa. Biogen and Elan argued that it should be moved to federal court to resolve whether the US Food and Drug Administration's approval shields drug makers from lawsuits.