I see that there’s an investment fund in Europe saying that “Every year, around 30 to 40 percent of the drugs approved by the FDA (U.S. Food and Drug Administration) were actually discovered in European academic labs“. Meanwhile the European Medicines Agency says that “Academia and other public-private partnerships helped to develop about 17% of the 94 products approved between 2010 and 2012“. And Médicines Sans Frontières is disputing some Pfizer advertising in the UK, saying that “tax payers foot much of the R&D bill through the funding and hard work that universities and government-funded laboratories do in actually discovering the compounds that are turned into blockbuster drugs“. Not to be outdone, I popped up yesterday saying that you could count the pure university-discovered drugs on your fingers. We can’t all be right. So it looks like it’s time to go over the real figures again.
The most comprehensive source for these remains this paper in Nature Reviews Drug Discovery by Robert Kneller, which covers the 1998-2007 period, and which I blogged about here and here. (I’m definitely not going to update its analysis while writing this blog post this morning, but I would like to do a bit of that for a future post).Kneller did a lot of work on this paper, and one of the things he did was assign each drug to a “main discovering organization” by going back to the original patent filings and publications. Looking at his supplementary Excel files, he has 252 drugs approved during that period. 117 of them were “standard NMEs (new molecular entities)”, that is, small-molecule drugs approved through the usual FDA process. Here are the ones that are primarily assigned to a university or similar:
1998: loteprednol (University of Florida)
1998: paricalcitol (University of Wisconsin)
1999: poractant (Karolinska Institute)
1999: doxercalciferol (University of Wisconsin)
1999: aminolevulinic acid (Queens University)
2000: cetrorelix (Tulane and Inst. for Drug Discovery-Budapest)
2000: cevimeline (Israel Institute for Biological Research)
2001: dutasteride (Tulane) Update: plenty of evidence for GSK here, so I’m removing it from the count below.
2001: galantamine (Mt. Sinai / Free Univ. Berlin)
2003: emtricitabine (Emory)
2005: exenatide (Mt. Sinai / Bronx VA Hospital)
2006: decitabine (Czech Academy of Science)
2006: docetaxel (CNRS, France) Update: added this one to the list; it’s a collaboration in the paper
2007: rotigontine (Groningen)
2008: lanreotide (Tulane)
That’s 14 out of 117 “standard” small molecules that don’t have drug-company fingerprints on their original discovery. The paper also breaks out 98 NMEs that were approved via priority review. Here are the ones that have a university, etc., as their primary discoverer, with no drug company in on that part:
1998: sacrosidase (Ludwig-Maximilien Univ. and Univ. of Connecticut)
1998: thalidomide, its revival (Rockefeller U. and Harvard/Children’s Medical)
1998: valrubicin (Dana Farber)
1999: ferric gluconate (Humboldt Univ. Berlin)
1999: nitric oxide (MGH and Karolinska Inst.)
1999: zanamivir (Monash Univ.)
2000: arsenic trioxide (2nd Shanghai Medical Univ. / Harbin Med. Univ.)
2000: vertiporfen (Univ. British Columbia)
2002: oxaliplatin (Nagoya City Univ.)
2002: oxybate (Univ. of Arkansas)
2003: enfuvirtide (Duke)
2003: abarelix (Indiana)
2004: pemetrexed (Princeton)
2004: apomorphine (Harvard/MGH , Brookhaven, Cagliari Univ., Univ. College London)
2005: tipranavir (Czech Academy of Science)
2006: vorinostat (Sloan-Kettering and Columbia Univ.)
2007: sapropterin (NIH and Nagoya Univ.)
That’s 17 out of 98, although I have to say that I don’t find all of those equally exciting, by any means. Some of them are slightly repurposed versions of things that had been known for a long time (although the revival of thalidomide certainly doesn’t fall in that category – that took some real imagination and spirit). This brings up a point mentioned in the NRDD paper, that the great majority of drug sales are actually from compounds discovered by the drug companies themselves. With some definite exceptions, the compounds listed above tend to be of lower impact. That may be partly because drug companies most definitely keep sales/medical need (those two are usually coupled pretty well) in mind when starting and continuing projects, and partly because some of the academic-derived compounds come under the “low-hanging fruit” category, such as the repurposing of apomorphine as a rescue therapy during severe Parkinson’s episodes (Apokyn).
You may notice that pregabalin isn’t on there, although perhaps it should be. It was listed in the spreadsheet as “Northwestern and Warner-Lambert” for earliest credit, though, and although the compound itself did come out of the Silverman lab there, the biology of it (mechanism of action, target, etc.) came out of the industrial work, and the original hypotheses turned out to be almost completely off. So that one is sort of a special case, although there are several other drugs that were also direct collaborations between academia and industry, and I’m sure that there are arguments to be made about each of them, in one direction or the other. The ones above, though, are the ones that you can say, pretty definitively, had completely academic origins – just the way that MSF is imagining it happening, to judge from their statements about Pfizer.
Now to the points in that first paragraph. These drugs represent more fingers than I happen to have, so my statement was indeed an exaggeration. I’ll update that post with a link to this one. Somewhere around 15% of the total approvals would be a more fair estimate, at least for the time frame this paper studied. Now as for that “thirty to forty per cent” coming from European labs, well. . .I sure don’t see it in the 1998-2007 data, that’s for sure.Even if you include all the joint-credit compounds not on the above lists, you don’t come anywhere close. I’ll see what it’s been like more recently, but I have my doubts. That 17% figure from the EMA might be more accurate, but even that’s high compared to this data set. Maybe those years were particularly rich? We shall see.