Post-marketing reports of liver toxicities in patients receiving multiple sclerosis drug Tysabri prompted a warning from Biogen Idec Inc. and Elan Corp. to physicians about monitoring patients for any signs of liver damage.

According to the companies' letter, posted on the FDA's website, reports of clinically significant liver injury, including elevated serum hepatic enzymes and elevated total bilirubin, both of which are predictors of severe liver injury, occurred as early as six days after the first dose of Tysabri (natalizumab). Signs of liver injury also have been reported for the first time after multiple doses and, in some patients, liver injury recurred upon rechallenge with the drug.

The news chipped shares of Dublin, Ireland-based Elan (NYSE:ELN) $1.54, or 6.3 percent, to close Wednesday at $22.77, while Cambridge, Mass.-based Biogen's stock (NASDAQ:BIIB) lost $1.40 to close at $60.13.

It's hardly the first spot of bad news for Tysabri, an alpha-4 antagonist that initially was approved in late 2004 in multiple sclerosis only to be yanked from the shelves a few months later after reported cases of progressive multifocal leukoencephalopathy, a fatal brain disease, were linked to the drug. The drug returned to the market in mid-2006 with a more restrictive label and Biogen and Elan have said no additional cases of PML have surfaced since its re-approval.

Concerns regarding liver toxicity arose during last year's advisory panel meeting on the supplemental biologics license application to expand Tysabri's use to Crohn's disease patients, but didn't prevent the panel from recommending approval. The drug gained the FDA's blessing in CD earlier this year. (See BioWorld Today, Jan. 15, 2008.)

Sales of Tysabri reached $229.8 million in 2007, and in its fourth-quarter earnings, Biogen executives said they aim to increase the number of patients on Tysabri to 100,000 by the end of 2010.