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Re: Guest Post - DNDi


Counterpoint. tl;dr: DNDi's work is founded on all that "waste" from large pharma, so if that goes away so does DNDi's model. Not that what they do isn't valuable, it's great and is a model for some of what my place hopes to do. Lowe is a little too laissez-faire capitalism for my tastes but does a good job of explaining drug development to a lay audience.
Note that HCV is related to Zika, all those spiked/wasted HCV projects are getting a strong second look now. But Zika really needs a vaccine- compound testing in indications affecting pregnant women sometimes require multigenerational studies.

Posted by: SP | Link to this comment | 09- 6-16 12:00 PM
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I'm not too excited about current science funding politics being applied in a hypothetical future to choosing which compounds get phase III trials, just in case anyone thought that I was the Polyanna.

I thought that numbers (even with reuse of pharma resources, getting a compound through trials is over $100M) were interesting, as well as the table listing successes and candidate compounds.

SP, do you know anyone who writes well about testing small molecules to choose candidates? I liked Juergen Drews' book a lot, but it's dated now.

I'm especially curious about whether there are real commercial efforts at personalized medicine-- compounds effective for only a particular genotype. As far as I know, the regulatory apparatus is basically not up to dealing with this approach to medicine at reasonable cost. I know a little about cutting-edge research hospital successes for personalized therapy for hard to treat cancers, but very small number of patients is tractable that way.

Posted by: lw | Link to this comment | 09- 6-16 12:33 PM
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Don't know any recent books that aren't very technical. Like I said if you want a blog Lowe is good at explaining the process whenever it comes up in the news.
There is definitely tons of work on personalized medicine and genetics. Obviously there are things already marketed, pairings of genetic tests and treatments (herceptin-herceptest). Genetics are being used in two ways for drug discovery- one is "experiments of nature" where people have a mutation that is beneficial or harmful for the same gene/pathway, and the beneficial ones that have no side effects suggest that the target would be safe in the general population that has no related mutation. We do a ton of that, working with companies to suggest new targets along those lines.
The other kind is more what you mean be personalized, and there are a couple approaches there. In some cases (Novartis) they use that as an entry to a focus application based on a genetic feature, then see if it can be broadened once they've established safety. Others try to look at existing medicines and identify biomarkers that suggest better application of them by targeted populations, we've done work in that area. Then there's developing to treat specific mutations, although it's not always mutations, more often profiles of multiple interacting genes or high expression or amplification of a particular gene.

Posted by: SP | Link to this comment | 09- 6-16 1:00 PM
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Technical is good. Yes, I read Derek Lowe's writings, like them a lot. He doesn't touch on economics much.

Herceptin is what I was thinking of. That required 2 rounds of trials, one for the compound and a second for the test. This regulatory approach at least doubles the cost of any personalized approached wrt older drugs. (Exact doubling if the failure rate of genetic tests to identify treatable subpopulation is the same as the failure rate for compounds).

There are a bunch of orphaned compounds with efficacy for many individuals but strong adverse effects for a subpopulation, adverse effects discovered during phase III. I'm curious about the existence of an economic pathway for identifying the variation relevant to the compound.

Posted by: lw | Link to this comment | 09- 6-16 1:38 PM
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Incidentally, I just finished my year-long course of Herceptin at the end of June, and I can say with complete sincerity that I thank God every day that it was developed. Less than twenty years ago, the prognosis for women with her2+ breast cancers was not very encouraging.

Posted by: J, Robot | Link to this comment | 09- 6-16 3:16 PM
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I assume you've read Billion Dollar Molecule? Also way out of date but entertaining to me since I know some of the characters.
Hmm, more recently, Rydzewski's Real World Drug Discovery seems to be frequently recommended although I haven't read it. The Emperor of All Maladies is good. The "What everyone needs to know" series has a book on personalized medicine, I'm familiar with the author's science. Francis Collins also published a book on it, he's a good writer.

Posted by: SP | Link to this comment | 09- 6-16 3:48 PM
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Posted by: sewa mobil di malang | Link to this comment | 09- 6-16 11:18 PM
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Speaking of neglected disease, woo Nature paper today.

Posted by: SP | Link to this comment | 09- 7-16 11:07 AM
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5. Congratulations, glad that you're here.
6. Thanks, looks interesting
8. Nice work, and nicely written, congrats. That's a huge number of initial screens to run!

Posted by: lw | Link to this comment | 09- 7-16 11:40 AM
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Posted by: sewa mobil malang | Link to this comment | 09-15-16 7:20 PM
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