Biogen’s Tysabri Causes Brain Infection In 2 Patients
16 CommentsBy Ed Silverman // July 31st, 2008 // 7:41 pm
Biogen and Elan have reported two confirmed cases of a deadly brain infection - progressive multifocal leukoencephalopathy - in patients taking their Tysabri multiple sclerosis drug, according to a filing with the Securities and Exchange Commission. Both patients were in the European Union, and were confirmed earlier this week. One remains hospitalized and the other remains clinically stable and ambulatory at home.
Biogen and Elan had pulled the drug from the market for a year after two other patients developed the infections, Bloomberg News reminds us. The FDA allowed sales to resume in July 2006 after deciding benefits for slowing MS relapses outweighed the risk.
oscar
The current risk management program has not mitigated the PML risk. What next?
B. Martin, MD
Although the following doesn’t matter to the rare individual who acquires PML…A risk-benefit analysis just published this week in Neurology (Thompson et al) indicates that the PML risk with Tysabri would have to increase more than 7 times to reduce the drug’s overall benefit below that of interferon beta. Tysabri wins out because it’s so much better at reducing relapses than interferon beta. See http://bmartinmd.com/2008/08/overall-riskbenefit-of-tysabri.html for more discussion.
HorusCat
Dr. Martin,
That’s a bit misleading, since there are no head-to-head trials with the interferons or glatiramir acetate. Researchers acknowledge that the relapse rate and apparent disease burden of patients entering trials in the past decade versus those who entered the pivotal interferon trials are far less. The APPARENT superiority of Tysabri is just that, APPARENT, until a head-to-head trial is done. Furthermore, to treat a non-fatal illness with a drug that can cause death raises ethical issues many physicians would rather avoid.
Were the TOUCH program adhered to, that would be one thing. But I have eyewitnesses to Biogen speakers and reps advocating the use of Tysabri outside of the TOUCH protocol–first-line or after only low-dose, low-frequency failure. That is a gross violation of regulatory guidelines on both the part of Biogen and the physicians who have chosen to use the drug off-label and outside of the standard of care.
Finally, since all on this site are so tuned in to conflict of interest, let’s make clear that most of the physicians using Tysabri own their own infusion centers–rendering their use of the drug quite profitable and their motivation for prescribing just a little murky.
atlex
As an addition to HC’s comment, Biogen/Idec and Elan do not participate in PhRMA and, therefore, do not necessarily follow the PhRMA code. HC points out that these companies may be conducting sales in a way that would get the major companies in trouble. BIO, the industry trade group for the biotech companies, needs to step forward and mandate that it’s members follow the same or a similar code of conduct. The reason it has never felt this pressure is that members of congress have been reluctant to attack this “high tech” industry.
HorusCat
atlex,
The prohibition against promoting off-label isn’t a pharma guideline–it’s a matter of law. I can’t remember the name of it, but it forbids making false (unproven or unapproved) claims about a product.
Adding further insult, I would assert, is the fact that many patients being counseled to go on Tysabri by physicians with financial COI have frontal lobe damage that may interfere with their judgment and decision-making processes. You could make a good argument that “informed consent” is not really possible in an MS patient who has suffered cortical lesions from the disease.
Justice in Michigan
HC - You are right that off-label promotion is against the law. At the same time, it is a law that is essentially never enforced. (With a few famous exceptions when there is a whistleblower and the press gets ahold of it and the FDA/DOJ is essentially forced to do something, as with Neurontin.)
Visit the recent thread on Zyrexa and scroll down to Doc’s post on the recent GAO report and posts that immediately follow.
The report is at:
http://www.gao.gov/new.items/d08835.pdf
As discussed in the summary on the thread, it is a law that functions according to an “honor system” - of which one would hope there was more.
ed silverman
Hi Folks,
For some background on the emergence of the GAO report, you can look at this post from last week, which also includes a link to the report…
http://www.pharmalot.com/2008/07/fda-fails-to-pursue-off-label-violations-report/
Cheers
ed
Justice in Michigan
Thanks, Ed. As has been noted, I think what is especially striking about the report - besides the length of time it takes for review and “remediation” (which means pulling the promo which co. anticipated doing anyway in the unlikely event they got busted), is the fact that _none_ of the eleven DOJ actions were initiated by FDA.
viz p. 2 of the report: “While FDA did not refer _any_ of these violations to DOJ for enforcement action, during calendar years 2003 through 2007, DOJ settled both civil and criminal cases that involved, at least partially, off-label promotion. These actions were initiated as a result of violations identified by sources _other_ than FDA and resulted in 11 settlements.” [emphases mine]
Thus, worse than Keystone Cops. No cops at all. And no actual prosecution; all settlements.
Among other things, this means that even if there _were_ a “fraud exception” under preemption (which there ain’t), none of the cases would qualify, because no convictions.
Ed Silverman
Hi Justice,
Yes, it would appear the GAO is saying that ‘W’ seems to always stand for whistleblower, at least in the context of this report.
ed
Justice in Michigan
Exactly. Soon the False Claims Act will also be repealed. And then people will be prohibited from opening their mouths about anything, since why have a talking President if what s/he says can be “second-guessed” by lay citizens?
All words have dangers.
harpy
atlex -
Any company - pharmaceutical, device, or bio - that sells in California is required to certify that they follow the PhRMA guidelines and have a “comprehensive compliance program” based on the OIG Guidelines - I’m surprised you don’t know this. That said, they do not always make this assertion easy to find.
Biogen Idec’s can be found here.
harpy
And here’s the link to the California Code, if you’re interested.
atlex
Harpy,
I am aware of California’s requirement, but the vast majority of those states do not have such a requirement. I am well aware that smaller pharmaceutical companies are able to fly under the radar with activities that would be against the PhRMA code. This includes biotechs. Moreover, Biogen-Idec’s code, as I read it, only apples to activities in California. For members of PhRMA, the code is a requirement throughout the country. It would be interesting to see BIO adopt a similar code of conduct.
Atlex
HorusCat
harpy,
I am not in CA, so what CA does is irrelevant to me in this case. Nonetheless, I would bet that the Biogen boys are up to no good out west.
Justice and others,
While the feds may not act on off-label promotion, my company IS acting. Keeping my job is a more immediate and compelling impetus to some reps than federal law to play by the rule book. And many, many doctors are more questioning of whether a claim is on-label or not. What irks me is that because smaller firms do indeed “fly under the radar,” I am selling with one arm tied behind my back–and increasingly, it feels like a gag in my mouth. I don’t want to sell off-label, but I would like to be able to raise points of fact from approved clinical articles; in its fear of federal retaliation, my company won’t let us do even that. The FDA scrutinizes the promotional efforts of some companies much more than others…
I find it ironic that there was such uproar about Neurontin, as benign a drug as it is possible to find (people take GRAMS and GRAMS of the stuff), while Tysabri is actually killing people and you hear nary a peep. AND it is expensive–isn’t using it outside of the TOUCH protocol fraud if Medicare Part D or Medicaid pays for it?
harpy
Are non-pharmaceutical companies even allowed to join PhRMA? Why would they? Is PhRMA lobbying for them? Actually, it doesn’t really matter does it - the PhRMA Code has no teeth, no punishment for breaking it, no reason to obey. It’s akin to saying one is moral simply because he attends church on Sunday. We belong to PhRMA, ergo we do no wrong - meh.
And are you saying that companies actually have a separate compliance program in California, and now Nevada, than they do for the rest of the states?
Beyond that, I’m surprised that two such staunch defenders of pharma are happy to attack a bio firm. A little internecine rivalry?
I do think FDA should have more power in pursuing off-label promotion cases, but not necessarily through the DoJ - according to the Washington Post, the DoJ has a 10 year backlog of whistleblower cases to deal with. Of the over 900 cases filed, more than 500 of them involve healthcare and pharmaceutical industries. So what does that say? Viva the PhRMA Code?
Bob Freeman
Harpy, yes, PhRMA has a number of Associate Member categories including CROs and PR firms. I tried to post a link but was unsuccessful; just go to PhRMA.org and a list is available.