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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

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March 10, 2014

Repurposing for Cervical Cancer

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Posted by Derek

One of the questions I was asked after my talk at Illinois was about repurposing drugs. I replied that there might be some opportunities there, but I didn't think that there were many big ones that had been missed, unless new biology/target ID turned up. Well, here's a news story that contradicts that view of mine, and I'm welcome to be wrong this time.

Researchers in Manchester have been working on the use of lopinavir (an existing drug for HIV) as a therapy for HPV, the cause of most cervical cancers. There's a vaccine for it now, but that doesn't do much for women who are already diagnosed with probable or confirmed disease. But lopinavir therapy seems to do good, and plenty of it. A preliminary trial in Kenya has apparently shown a very high response rate, and they're now raising money for a larger (up to 1,000 patient) trial. I hope that it works out as it appears to - with any luck, HPV-driven disease will gradually disappear from the world in the coming decades, but there will be plenty of patients in the meantime.

As that Daily Telegraph article shows, it wasn't easy getting this work going, because of availability of the drug in the right formulation. Congratulations to the Manchester group and their collaborators in Kenya for being so persistent.

Comments (6) + TrackBacks (0) | Category: Cancer | Clinical Trials | Infectious Diseases


COMMENTS

1. RTW on March 10, 2014 8:32 AM writes...

Thalidomide as you may recall has been repurposed for multiple Myeloma, and as a treatment for leprosy. This is not a new thing by any means. I believe many companies screened some of their existing drugs against other indications, when data suggested that this might yield additional products in the pipeline. There just were not many uncovered so far.

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2. jbosch on March 10, 2014 9:00 AM writes...

Here's another one - that also questions the "few" millions spent on Biodefense. They screened Bacillus anthracis; Francisella tularensis; Coxiella burnetii; and Ebola, Marburg, and Lassa fever viruses

PLoS One. 2013;8(4):e60579. doi: 10.1371/journal.pone.0060579. Epub 2013 Apr 5.
A systematic screen of FDA-approved drugs for inhibitors of biological threat agents.
Madrid PB1, Chopra S, Manger ID, Gilfillan L, Keepers TR, Shurtleff AC, Green CE, Iyer LV, Dilks HH, Davey RA, Kolokoltsov AA, Carrion R Jr, Patterson JL, Bavari S, Panchal RG, Warren TK, Wells JB, Moos WH, Burke RL, Tanga MJ.

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3. mrabbit on March 10, 2014 10:01 AM writes...

It would be surprising if HPV exists only in the cervices of the women "cured" by using lopinavir as a pessary. One would suspect that there will be recurrence.

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4. CMCguy on March 10, 2014 10:57 AM writes...

Are not many of the existing HIV antiviral drugs build upon re-purposing of unfulfilled protease inhibitor R&D programs? Most of major Pharmas were heavily in that area in the 80s chasing a number of potential targets and a few may have gotten as far as early clinical studies although do not know if any ever became drugs however recall interest was waning. A combination of events in late 80s converged to point to the same structural class as inhibitor of HIV and pressures to come up with treatments lead to atypical discovery and development timelines that the industry wishes they could duplicate now.

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5. pt on March 10, 2014 10:59 AM writes...

It should be noted that the case is an example of "on-target" repurposing where the drug has been previously known to bind the target. This is in contrast to "off-target" repurposing where the drug is found to be active against a completely different target.

Almost all cases of repurposing are "on-target" or cases where the new target is very closely related to the existing known one.

This shouldn't come as a surprise. Most drugs have been optimized to bind their intended primary target in the nanomolar range. It is very unlikely that one would later discover an unrelated target which the drug would bind with a comparable affinity.

Binding an unrelated target with a orders of magnitude lower affinity is less rare. This would, however, require further optimization of the ligand structure for the drug to have a beneficial effect. But then we would not be talking about drug repurposing anymore.

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6. ajsp on March 12, 2014 5:35 AM writes...

Be very careful with the Telegraph as a source of new in general, and science news in particular.

I don't know about the american press, but here in the UK the general press tend to be pretty weak on science, and the Telegraph is far from a shining example. Only the Economist/FT seem to avoid falling into the 'embarassing' category too regularly; the Guardian can be good, but is a very mixed bag.

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