Tysabri Linked to PML Again

  • Tysabri has been in the news again this week.  Last Friday the European Medicines Agency (EMEA) announced that they would review the benefits and risks for Tysabri.


    The Committee started a review of the benefits and risks of Tysabri, in view of reports of 23 cases of progressive multifocal leukoencephalopathy (PML) worldwide since Tysabri has been on the market. This review is initiated to discuss any additional measures necessary to ensure the safe use of Tysabri and how to balance the risks to the patients against the benefits of the treatment. Tysabri is indicated for patients suffering from highly active relapsing remitting multiple sclerosis with high disease activity despite treatment with a beta-interferon and for patients with rapidly evolving severe relapsing-remitting multiple sclerosis.

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    This information hit the stock market on Friday, affecting the stock prices of Elan (ELN) and Biogen Idec (BIIB).  Then it was spread by various news channels and MS organizations on Monday.  Drowned in the minor uproar was an announcement that a 24th patient had developed progressive multifocal leukoencephalopathy following Tysabri use which was reported to EMEA on Sunday. 


    Interestingly on Tuesday, articles started coming out which either blamed European doctors on the increase in PML cases or touted a revival strategy for the use of Tysabri involving a test for the JC Virus which causes PML.  And to cap off the news alerts and search engine results for folks looking for recent news regarding Tysabri, Elan and Biogen choose this time to announce that Tysabri use in Crohn's Disease cuts hospitalization rates.


    Last week before this latest round of announcements and articles appeared, Tysabri was discussed at length during a conference call conducted by Biogen Idec.  Here's an excerpt from the Motley Fool article - All Tysabri, All the Time.


    Increasing the number of patients on the drug may only get harder, though. On the conference call, management said that Elan and Biogen now believe that the risk of developing progressive multifocal leukoencephalopathy (PML), a potentially deadly brain infection, increases with the number of infusions a patient receives. Biogen is in discussions with the Food and Drug Administration to update the label to reflect this new belief.


    The change could result in patients taking breaks from Tysabri, perhaps going onto other medications and then returning later. Just realize that drug holidays for patients result in revenue holidays for Biogen and Elan, so they're definitely not a reason to celebrate with friends and families.


    Also on Friday, Bloomgberg reports that the Food and Drug Administration (FDA) confirmed the number of PML cases.  Note that as of Sunday, this information is already somewhat out-of-date with the report of the 24th case of the (potentially lethal) brain infection.  Here is an exerpt from Biogen, Elan Fall as Tysabri Brain Disease Cases Rise.


    The FDA confirmed there have been 23 cases of PML in Tysabri patients since marketing of the drug resumed in 2006, Karen Riley, a spokeswoman, wrote in an e-mail today.


    “The FDA continues to receive reports of PML cases in real time and we are monitoring the incidence of PML both in the United States and worldwide on an ongoing basis,” Riley wrote. “The agency is continuing to assess the issue to determine the need for further regulatory action.”

    The new cases reported in Europe may push the total number of Tysabri patients who have contracted PML above the infection rates currently discussed on the U.S. label for the medicine, said Yaron Werber, an analyst with Citigroup Global Markets Inc. in New York, in a note to clients today.

    If the patients were on Tysabri for more than a year and fewer than two years, the rate is below the 1 in 1,000 indicated on the U.S. label, Werber said. If all of the patients were taking the therapy for two years or longer, the infection rate would be “an alarming 1.42 out of 1,000,” Werber said.

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    “If the rate creeps substantially above 1 out of 1,000, it is possible that regulatory agencies may consider more severe measures,” Werber said.


    Niamh Lyon, an Elan spokeswoman, said in an interview that it would be “imprudent” to speculate or comment on regulatory discussions or their potential outcomes.


    What this means is that for those patients who have had more than two years of Tysabri infusions, the risk of developing PML looks to be closer to 1:700 (or I've even seen mention of 1:400).  But we do not have all of the information to be able to make those calculations.  In July 2009 Biogen and Elan ceased making public announcements when each case of confirmed PML was reported to them.  As of 30 Sept, an estimated 46,000 people globally were taking the drug, which is a major source of revenue for both Elan and Biogen Idec.


    Basically, it's difficult to know exactly what the details are since the reports vary greatly depending upon whether the article is geared to be positive or negative.  Slant seems to permeate and dominate the media now-a-days.


    If you read any of the other MS message boards, then you can certainly find discussion of Tysabri, its benefits and its risks.  There are patients who are thrilled with how Tysabri has benefited them.  There are patients who are concerned with the risks and perhaps more so with the lack of transparency regarding new information arising around those risks.


    Right here at MS Central, patients have asked questions about side-effects of the infusions, looking for others who may have experienced the same things.  The discussion of those side-effects is lacking on most MS message boards, it seems, because the Tysabri advocates dominate the discussion and spend time in argument with those who discuss the risks in general (not personal) terms.


    I can't speak to the side-effects because I haven't tried Tysabri and have had a difficult time sorting through stories from other MSers to gain a better understanding of their experiences.  Of the over 60,000 patients who have tried Tysabri a significant percentage no longer use it for whatever reason (side-effects, antibodies, lack of efficacy, etc).


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    The one thing which is positive about all of the discussion around Tysabri use is that I learned (from other patients) that I would not be a candidate for its use.  Why?  Because I use methotrexate to treat my rheumatoid arthritis.  Many of the patients who have developed PML were immunosuppressed due to use of drugs such as methotrexate, cytoxan, imuran, etc.  I am thankful to know this information and to be able to pass it on.


    Score ONE for the patient community in educating others within the community!!


    Lisa Emrich is author of the blog Brass and Ivory: Life with MS and RA and founder of the Carnival of MS Bloggers.

Published On: October 29, 2009