Drug Discovery — Even When You Win, You Still Can Lose
    By Josh Bloom | February 11th 2014 03:21 PM | 10 comments | Print | E-mail | Track Comments
    About Josh

    Director of chemical and pharmaceutical sciences at The American Council on Science and Health in New York since 2010.

    Former research chemist


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    It would be almost impossible to find a better example of the difficulties that face the pharmaceutical industry than the campaign against hepatitis C.

    Unfortunately, this example is now at the expense of Vertex Pharmaceuticals, a small, but top-notch drug discovery organization that began as a biotech startup in 1989.

    Vertex had the “good” fortune of becoming the first drug company to launch a successful antiviral drug, which had a real impact on hepatitis C—a disease with enormous worldwide public health implications. But, within a year, their fortunes turned sour.

    Called “The Silent Killer,” the viral blood-borne disease infects the liver, progressively doing irreversible damage over a two- to three-decade period. Most people who are infected are unaware of this until symptoms of liver disease show up, at which time the resulting cirrhosis or liver cancer are life threatening.  The majority of liver transplants in the U.S. are due to liver failure caused by long-term hepatitis C infection.

    Although hepatitis C is much less newsworthy than HIV, the worldwide infection rate is estimated to be four percent—about four-times greater than for HIV. With an estimated 150 million infected people worldwide, the disease became the focus of most infectious disease research beginning in the mid-1990s—surpassing even HIV in research effort.

    Virtually every major drug company launched massive research campaigns designed to discover specific antiviral therapies to eradicate the infection. It was far more difficult than anyone could have imagined.

    Although researchers used a very similar strategy that was supremely successful for HIV, hepatitis C proved to be a much tougher nut to crack.

    Indeed, after a decade of research, and dozens of drug candidates that failed because of toxicity or lack of efficacy, in 2004, scientists at Boehringer Ingelheim in Quebec hit the jackpot—or so it seemed. Ciluprevir—the product of arguably one of the most impressive campaigns in the history of medicinal chemistry—was shown to reduce the amount of the virus in the blood to nearly zero after a few doses.

    However, unexpected cardiac toxicity forced the discontinuation of the development of the drug. Even though Ciluprevir provided the first proof of principle that a specific antiviral drug could essentially wipe out the virus, this must have been little comfort for Boehringer.

    It would be another seven years until the first HCV drugs would be approved. Within two weeks, Vertex Pharmaceuticals and Schering-Plough (now Merck) both launched improved versions of Ciluprevir.

    Vertex’s drug, Incivek was superior to Merck’s Victrelis, and it captured essentially the entire anti-HCV market, with sales of an astonishing $457 million in its first full quarter.

    But then things went downhill. Given the enormous (and scientifically brilliant) effort that Vertex put forward to discover Incivek, it is perfectly fair to expect them to be financially rewarded. But life is not always fair—especially in the pharmaceutical world.

    What went wrong?  The efforts of other companies working in this area (especially AbbVie, Gilead, Johnson and Johnson, and Bristol-Myers Squibb)—although a bit behind Vertex—were beginning to pay off. Clinical results have been astounding, with cure rates approaching 100 percent with certain drug combinations. And aside from the exquisite efficacy of these newer drugs, one enormous advantage is that interferon—an injectable immune stimulant that is still part of the standard of care—can be avoided. This is critical because the side effects of interferon are so brutal that many patients discontinue treatment, essentially committing pharmaceutical suicide.

    Now, doctors are advising their patients to wait until some of these second-generation drugs are approved, and this has had a profound impact on Vertex. Sales have plummeted to $86 million this past quarter, and the company just announced a staff reduction of 370 employees—15 percent of its workforce.

     This perfectly illustrates two points: 1) Even when a drug goes through a 10-year approval process and makes it out the other end, it still may lose money. In fact 70-80 percent of marketed drugs do just that; 2) Perennial critics of the pharmaceutical industry, such as Marcia Angell of the Harvard Medical School, who maintain that second- and third-generation drugs (often derisively ‘called me-too drugs’) are unnecessary and serve only the companies that make them, must be living on another planet. Because on this planet the first drug for any given disease is rarely the best.

    Had research and development ceased after the introduction of Incivek, therapy for hepatitis C would have remained difficult to endure, and less than optimally effective.

    There is no tougher business than drug discovery. You can win the race and often still come out the loser.

    Update 2/11/14: Gilead is now seeking approval for their drug combo consisting of  Sovaldi and ledipasvir—two potent anti-HCV drugs that work by different mechanisms (like the AIDS cocktail approach). This will be the first non-interferon therapy for the infection. 

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    Josh Bloom
    OK. Since no one else commented on the damn thing I guess I better do it myself.An absolute masterpiece!
    Josh Bloom
    It was good, clear, well-written a cited. Thankyou.
    More please.

    Josh Bloom
    Thanks much.Josh
    Josh Bloom
    Perhaps there aren't a whole lot of people out there who are dumb enough to fall for your tired "oh shucks guys, we're' just trying to make a living here" schtick for one of the most profitable industries in the history of the world, an industry that refuses available solutions to problems simply because they can't patent them to make filthy, exclusive profits. And perhaps everyone is all too familiar with the fact that you're just a shill and we know that shills are going to write a biased article.

    Josh Bloom
    I figured that if this piece was visible for awhile I would get a few fools to comment on it.  Congratulations, you're the first.  
    Let's examine your claims:  
    1) Why exactly would I be shilling for an industry that threw me (and all of colleagues) out on our behinds in 2010?  Most of us never got another job in the industry and never will.  And keep in mind that neither I nor my current organization gets a single penny from a pharmaceutical company. Please explain how this is shilling.
    2) What available solutions are you talking about?  Because if a company (or even an individual) came up with a new use for an old drug (or anything else, really), it would be patentable. Whatever brilliant idea you're talking about, go patent it yourself. In the (extremely) unlikely event that whatever you came up with was really good for something or ever, then you could sell it to a company and you could make the "filthy profits."    
    3) Speaking of which, correct me if I'm wrong, but you seem to be saying that the world would be a better place if drug companies did *not* discover and develop AIDS and HCV drugs that will save millions of lives. Go read some news stories from the early 1980s and see what it was like back then. Do you *really* believe that it is worse to have expensive, effective drugs than none at all? Please explain this too.    
    This ought to be interesting. 
    Josh Bloom
    Yes Josh you're probably the only expert on that topic. One think though, I shared your article in facebook and the title did not come out.  Please check. It is important in order to improve the coverage of readers and , eventually, ( you might) get some comments.

    Josh Bloom
    CamiloNot sure what you mean by "didn't come out."
    This is the first time I've written anything here, so it may be that I screwed something up.
    Thanks for letting me know.
    Josh Bloom
    Facebook's parser for URLs can be inconsistent - they are always fixing things, even if they don't need fixed. I have had that happen to me also but next time it should be okay.
    Bonny Bonobo alias Brat
    There is no tougher business than drug discovery. You can win the race and often still come out the loser.
    Very interesting article Josh and beautifully written I thought. I guess that like any race the outcome for the participants depends upon the rules and if there are no rules or too few rules or even unfair rules then anarchy or injustice is likely to result. Too many rules can also handicap everyone concerned, the pharmaceutical industry and the cost of their investments in research as well as the patients who desperately need good drugs. Not sure what the solution is but its definitely a problem :(
    My article about researchers identifying a potential blue green algae cause & L-Serine treatment for Lou Gehrig's ALS, MND, Parkinsons & Alzheimers is at
    Josh Bloom
    Helen-   Thanks much. Very nice to hear
    Josh Bloom