Reuters Nails Pharma Jobs Frustration But Misses On Biologics, Small Molecules

This AM, Reuters released a special report about the state of drug R&D. Overall, I enjoyed reading the piece. Though there isn't a whole lot in there that C&EN's readers who work in the area won't already know, I think the article does a great job of capturing how scientists- and young scientists in particular- feel about their job situation. The folks quoted in the article are feeling more than a little frustrated. That said, there were a couple of statements in this article that were unfair, misleading, or downright pessimistic. In the section on biotech, we have this generalization:
Biotech's "large molecule" protein drugs, made using genetic engineering, have proven superior at fighting complex diseases like cancer to many conventional "small molecule" chemical drugs.
That argument is a little hard to swallow. You might say that the side effects from a protein drug are more benign than those of traditional chemotherapies like 5-fluorouracil. And Herceptin, a biologic drug, has made a big difference for women with a specific type of cancer. But what about Gleevec? If you have cancer driven by a certain genetic mutation, Gleevec works-and it's a small molecule. Look closely at Herceptin or Avastin-a biologic cancer drug the Reuters article mentions in its next paragraph- and you'll notice that for treating some cancers they must be taken with small molecules- carboplatin, paclitaxel, or something else. Both parts of the treatment- the small molecule and the protein- are necessary for the treatment to work its best. Maybe cancer isn't the best example- after all, every cancer is a different challenge. What about other diseases? In the past, we'd written about how biologic drugs are the best we've got for multiple sclerosis. Humira, a biologic treatment for rheumatoid arthritis, is another success story that the Reuters article mentions. But what about HIV? There are an awful lot of small molecules on this list of approved HIV drugs, and when used correctly, they keep the disease at bay for years. Yes, there's some wiggle room in the Reuters statement because of the use of the word "many". Maybe it's the organic chemist in me speaking, but I get pretty miffed when I hear pessimistic statements about small molecules. A smaller nitpick but a nitpick nonetheless- the article seems to use the words "biotech" and "biologic" interchangeably, which might confuse someone who isn't familiar with the area.
By 2014, the world's two top-selling prescription drugs won't be tablets sold in blister packs but needle-based biotech treatments -- Avastin for cancer, sold by Roche, and Humira for rheumatoid arthritis, from Abbott Laboratories -- according to consensus forecasts compiled by Thomson Reuters.
Lastly, I wish the article hadn't ended back in an academic setting. Instead, I would've liked to hear more about the scientists who migrated to Parexel, the company that conducts clinical trials for drugmakers. That academic ending was a downer to me- it represents a narrow-minded view about what the skills of a scientist trained to work in pharma are good for.

Author: Carmen Drahl

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  1. Biological drugs are hot right now and the hype factor is huge. Certainly the hope has always been that they would be exquisitely selective and thus offer the true “magic bullet” effect.

    We have learned, though, that the supposed “dirtyness” of small molecule drugs often is essential to their effectiveness in vivo. It just makes sense. Biological systems, especially in humans, are complex and often have multiple redundant systems to compensate if the execution of a single biological step is disrupted. Drugs that work well in the real world block that step and also happen to muck up a compensating pathway. Generally this happened by accident rather than design, but still it can happen! Biologics rarely do that. They are selective and in some cases that selectivity will actually LIMIT their effectiveness.

    Bioavailability and drug delivery are also issues for biologics. Most people think that small molecules will always be important in drug therapies.

  2. True that, partialagonist. I would imagine that plenty of drug companies would like to follow a biologic product with a small molecule product aimed at the same target… for all the reasons you state, not to mention complexity, especially where glycoproteins are involved. That’s not always been possible, of course. And in some cases, you have the times when the complex drug is cheap (cough-heparin-cough).