I have two problems with the news, out of Kenilworth, tonight, that a study at Duke (funded by Schering-Plough) has likely-identified the gene variant which dictates that current Hep-C treatments are largely ineffective in many people of color. [My backgrounder -- on this sad state of affairs -- here.]
I am always in favor of learning, and knowing, more -- don't misunderstand -- but I am surprised that both the PI, and the press reports (see below) characterize the (predominantly) African Americans' gene sequence as containing a "spelling mistake" -- when in fact, the mistake (if there one be) is that our current standard treatment (here, Schering-Plough's $915 million a year franchise) fails to address a very common biological variant.
My second concern is that this new test will be used by diagnostic companies, that sign license agreements with Schering-Plough (as owner of the IP), to encourage doctors to keep more patients on standard regimens, when it is shown that they are likely to respond to treatment (i.e., in the stilted-language of the researchers -- have no spelling errors in their alleles -- near Interleukin-28B).
My understanding is that the next generation of Hep C treatments -- primarily Vertex's teleprevir -- is not dependent on this gene variant receptivity. In fact, as I understand it, should Vertex win FDA approval for teleprevir, much of Schering-Plough's $900 million per year franchise becomes "trailing edge". Some of Schering's current offerings will still be prescribed with teleprevir, but at nothing like the pace now seen.
So, this hub-bub about a test may be used to delay the transfer of Hep C non-responders into Vertex-sponsored teleprevir investigational studies -- or at least I fear that sad outcome. What do you think? Let me know -- in the comments. Here is the Reuter's version of the story -- and a pull-quote, from it [emphasis supplied]:
. . . .Hepatitis C is a blood-borne liver disease that can lead to chronic liver problems, liver cancer, cirrhosis and death. The virus affects an estimated 3.2 million people in the United States alone and 170 million worldwide.
Treatment typically involves 48 weeks of interferon plus the antiviral drug ribavirin. Some patients develop such taxing side effects that they stop treatment. Blacks are less likely to respond than whites.
Until now, no one has known why.'SPELLING MISTAKE'
According to Goldstein's study, published in the journal Nature, it may be because of a "spelling mistake" -- a one-letter error in the genetic code near the Interleukin-28B or IL28B gene, which plays a role in fighting off infections.
"If you look at individuals with the good response genotype, about 80 percent of them will be cured. If you look at individuals with the poor-response genotype, about 30 percent of them will be cured," Goldstein said in a telephone interview. "That is just a huge, huge difference."
The discovery came from a clinical trial of 1,671 people with the most common form of the disease in the United States and Europe who were taking the two most common hepatitis C therapies.
It was funded by Schering-Plough, maker of one of two standard hepatitis C regimens. . . .
A spelling mistake? Really? Why is it that the less dominant, "TT" allele, at IL 28B, is a "mistake"? C'mon, now FDA -- let's get Vertex's teleprevir to market STAT! [or, ASAP, if one prefers.]
LATER: The New York Times does a better job with the story -- correctly pointing out that this is likely the result of either milder strains of hepatitis (or similar viral agents) in ancient Africa, or of more potent ones in East Asia, and to a lesser extent, Europe, in our collective, but very-distant, evolutionary past.
7 comments:
Agreed. Africans tend to have older genetic sequences, therefore if 'mistakes' occur they are more likely to be present in other populations (e.g. Cystic Fibrosis) or are more prevalent in a particular population as they confer a survival advantage in that particular population, which may otherwise be detrimental (e.g. sickle cell trait).
Yes mistakes do occur but evolution will determine if they are advantageous to survival or not. Lacking an advantageous 'mistake' is not in an of itself a 'mistake' and reflects a personal bias. I would not however presume such a bias is intentional as all individuals and groups will often look at themselves in a positive bias.
Salmon
Fair enough, Salmon.
As ever, yours is a reaonable voice.
I was encouraged to see that the study's PI had a more scientific set of quotes, in the New York Times article (final link, above).
That would lead me to believe, in turn, that much of the plainly-biased "mistake" metaphor was a result of the Reuters' writer trying to "dumb-down" a complex concept, not (so much) the PI's actual views.
As I say -- that is encouraging.
In any event, natural selection, and variation, is why these things are the way they are -- not any Supreme Being's "mistake" -- at least in my view.
As you no doubt know, Olduvai Gorge, and its sister site, Laetoli, are likely the cradle of us all -- and each is, in fact, in what we now call Tanzania -- Africa. So if one were to press the mistake metaphor, one would have to say that the "errant" copies were made not in the cradle, but on the various playgrounds, and middle schools -- in East Asia, and Western Europe -- perhaps less than 100,000 years ago.
But that would be (far) too much, about too little. . . .
Namaste
Thank you. You said it more explicitly than I did. As I pointed out mistakes such as Cystic Fibrosis are more likely to occur in Europeans.
We pharmaceutical scientists have been studying these genetic variations for years. Some going back to articles in NEJM or other prestigious journals to the late 1950's.
There a many drugs where we know the risks of certain things are higher just based on ethnicitiy. e.g. agranulocytosis with clozapine in Israelis vs. pancytopenia in Thai, Stevens Johnson's in Han Chinese with the highest incidence in Taiwan and second in Bangkok. N-acetyltransferase variation being dependent on geography with slow acetylators most prevalent in saudi arabia. High CYP3A5 activity in african americans.
Many of these variations are known to either increase drug toxicity or decrease efficacy or both. Yet rather than tell practicing docs' Oh Use anticancer drug B as it isn't effected by this genetic variation but don't use anticancer drug A because your african american patient won't only not get any benefit but they'll die horrible deaths from the toxic metabolite. We're silent. Instead we wait until we can sell these little tests to make even more money. What do you think FDA commissioner really has in mind when he talks about the promised of personalized medicine.
It make me sick with what I see going on. I wish I could find a Qui Tam lawyer I know where there is billions in fraud that's being left on the table.
Salmon
Funny you should mention Qui Tam.
Seriously -- maybe we should talk (off-line).
Namaste
I would like that. The question is how do we get in contact?
I suspect that there are a couple of people who may know how to contact you ES? MM?
Salmon
Both do. I'll tell MM that MM may pass my email to you -- or you may pass yours, to MM. Then I'll have it. Sorta' like a trusted key pair, eh?
Better than 128-bit, or 256-bit encryption. . . .
Again, thanks for everything!
Namaste
Salmon -- there should be one in your email box, now -- from some goof named "Condor". . . I dunno' him; really. I don't.
Namaste
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