FDA Adverse Event Reports Show Tysabri May Be Tied To Other Serious Side Effects
On August 29, 2005 The Wall Street Journal ("WSJ") reported that a list of adverse event reports made to the FDA related to the Tysabri included several rare infections, some of which were fatal, apart from the rare brain infection called progressive multifocal leukoencephalopathy.
Tysabri, a multiple-sclerosis drug, was withdrawn from the U.S. market on February 28, 2005 due to increasing concerns that Tysabri use could cause progressive multifocal leukoencephalopathy ("PML"). At that time, the companies responsible for Tysabri, Elan Corp. of Ireland and Biogen Idec Inc. of the U.S., said two patients with multiple sclerosis ("MS") taking Tysabri had contracted PML, with one patient dying from PML. The two companies later confirmed a second fatal case of PML in a patient using Tysabri to treat Crohn's disease, a gastrointestinal disorder.
The new WSJ article is based on information obtained through a Freedom of Information request made to the FDA by an pharmaceutical industry analyst at Morgan Stanley, Steven Harr. Following an analysis of the Tysabri data which he received from the FDA, Mr. Harr issued a report on August 25, 2005 describing some adverse event reports for Tysabri which showed a number of Tysabri patients had died of rare infections. "We're not trying to put a death knell on Tysabri, but there are signals in there that something's going on. It's important for patients and investors to know," Mr. Harr said in an interview.
A spokesman for Biogen immediately dismissed Mr. Harr's report, stating that Biogen and Elan had performed a detailed safety analysis of Tysabri. The companies' analysis, according to this spokesman, found no statistically significant differences between serious adverse events with patients given Tysabri and patients given a placebo in several clinical trials. "We have an enormous amount of information in our hands," the spokesman said. "The [FDA's adverse event reports] database is a limited tool."
According to the WSJ article, by staff reporter Sylvia Pagan Westphal:
The analyst's report describes seven non-PML deaths in patients taking Tysabri that "appear to be related to immunosuppression." One death was owing to pneumocystis pneumonia, an infection that only patients with severely debilitated immune systems get; another was because of herpes encephalitis, a rare infection of the central nervous system. Four other deaths were possibly caused by sepsis, an uncontrolled infection that spreads through the body. The report mentioned that the FDA database contained "numerous" accounts of serious, nonfatal infections that "suggest again that the toll from Tysabri extends beyond PML."
Despite the problems that may be posed by these possible new side effects, Mr. Harr predicted that Tysabri has a good chance of returning to the market. In fact, Biogen and Elan said earlier in August 2005 that they hope to get the drug back on the market. The companies announced, then, that they had screened more than 2,000 MS sufferers who took Tysabri in clinical trials for signs of PML. According to the companies, the screening produced "no new confirmed cases" of PML.
Lars Ekman, executive vice president and president of research and development at Elan, had this comment:
Patient safety remains our top priority.... We are committed to finalizing the safety evaluation for Crohn's disease and rheumatoid arthritis, which is progressing well and on track to be completed by the end of the summer. We look forward to working with regulatory authorities to determine the path forward for Tysabri.
Given these new adverse event reports of other serious infections in Tysabri users other than the rare brain infection PML, there seems to some choppy waters ahead for Biogen and Elan as they try to get Tysabri back on the market.
(Posted by: Tom Lamb)