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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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January 21, 2013

That Many Compounds in Development? Really?

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Posted by Derek

So PhRMA has a press release out on the state of drug research, but it's a little hard to believe. This part, especially:

The report, developed by the Analysis Group and supported by PhRMA, reveals that more than 5,000 new medicines are in the pipeline globally. Of these medicines in various phases of clinical development, 70 percent are potential first-in-class medicines, which could provide exciting new approaches to treating disease for patients.

This set off discussion on Twitter and elsewhere about how these number could have been arrived at. Here's the report itself (PDF), and looking through it provides a few more details Using figures that show up in the body of the report, that looks like between 2164 compounds in Phase I, 2329 in Phase II, and 833 in Phase III. Of those, by far the greatest number are in oncology, where they have 1265, 1507, and 288 in Phase I, II, and III, respectively. Second is infectious disease (304/289/135), and third is neurology (256/273/74). It's worth noting that "Psychiatry" is a separate category all its own, by the way.

An accompanying report (PDF) gives a few more specific figures. It claims, among other things, 66 medicines currently in clinical trials for Hepatitis C, 61 projects for ALS, and 158 for ovarian cancer. Now, it's good to have the exact numbers broken down. But don't those seem rather high?

Here's the section on how these counts were obtained:

Except where otherwise noted, data were obtained from EvaluatePharma, a proprietary commercial database with coverage of over 4,500 companies and approximately 50,000 marketed and pipeline products (including those on-market, discontinued, and in development), and containing historical data from 1986 onward. Pipeline information is available for each stage of development, defined as: Research Project, Preclinical, Phase I, II, III, Filed, and Approved. EvaluatePharma collects and curates information from publicly available sources and contains drug-related information such as company sponsor and therapy area. The data were downloaded on December 12, 2011.

While our interest is in drugs in development that have the potential to become new treatment options for U.S. patients, it is difficult to identify ex ante which drugs in development may eventually be submitted for FDA approval – development activity is inherently global, although regulatory review, launch, and marketing are market-specific. Because most drugs are intended for marketing in the U.S., the largest drug market in the world, we have not excluded any drugs in clinical development (i.e., in Phases I, II, or III). However, in any counts of drugs currently in regulatory review, we have excluded drugs that were not filed with the FDA.

Unless otherwise noted, the analysis in this report is restricted to new drug applications for medicines that would be reviewed as new molecular entities (NMEs) and to new indications for already approved NMEs. . .

Products are defined as having a unique generic name, such that a single product is counted exactly once (regardless of the number of indications being pursued).

That gives some openings for the higher-than-expected numbers. For one, those databases of company activities always seem to run on the high side, because many companies keep things listed as development compounds when they're really ceased any work on them (or in extreme cases, never even really started work at all). Second, there may be some oddities from other countries in there, where the standards for press releases are even lower. But we can rule out a third possibility, that single compounds are being counted across multiple indications. I think that the first-in-class figures are surely pumped up by the cases where there are several compounds all in development for the same (as yet unrealized) target, though. Finally, I think that there's some shuffling between "compounds" and "projects" taking place, with the latter having even larger figures.

I'm going to see in another post if I can break down any of these numbers further - who know, maybe there are a lot more compounds in development than I think. But my first impression is that these numbers are much higher than I would have guessed. It would be very helpful if someone at PhRMA would release a list of the compounds they've counted from one of these indications, just to give us an idea. Any chance of that?

Comments (21) + TrackBacks (0) | Category: Clinical Trials | Drug Development


COMMENTS

1. Boghog on January 21, 2013 10:02 AM writes...

an unnecessarily complicated phrase:

"identify ex ante" = predict

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2. Ed on January 21, 2013 10:03 AM writes...

I think you can safely divide all those figures by two....where I used to work (small UK biotech) about half of all compounds listed in the pipeline are zombies. I reckon that is pretty typical (although n=1), especially since the funding crunch of 2008.

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3. Morten G on January 21, 2013 10:06 AM writes...

Close the damn italics.
Please.

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4. Derek Lowe on January 21, 2013 10:24 AM writes...

Damn italics now closed.

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5. hpack on January 21, 2013 10:30 AM writes...

"...and to new indications for already approved NMEs. . ."

Doesn't that phrase imply that every currently marketed drug that is in a trial for a new indication is counted once? I'm not sure how many that would account for, but just about every on-patent marketed oncology drug is currently in trials for additional indications.

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6. Boghog on January 21, 2013 11:18 AM writes...

@2: "half of all compounds listed in the pipeline are zombies"

As a biotech's market cap is directly related to the number of compounds in the clinic, I think your explanation for the inflation is spot on.

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7. pgwu on January 21, 2013 11:29 AM writes...

Big pharma AA has one drug in development in collboration with startup Biopharm aa. Bigger pharma BB collaborates with AA. All claim the drug to give public the impression of three drugs under development while in reality there is only one.

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8. simpl on January 21, 2013 11:48 AM writes...

The HIV figure of 145 would seem to include combinations with existing compounds - that might also be the case in oncology too

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9. Caltech Grad Stduent on January 21, 2013 12:45 PM writes...

There are at least 30 PI3K inhibitors in clinical trials. All are 'first in class' because there is no drug hitting PI3K approved yet.

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10. bio_kruncher on January 21, 2013 1:19 PM writes...

While the total probably includes some drugs not in active development, it does not seem excessively high to me.
Consider some of the following. I don't have time to look up latest numbers for all of these but in past have been able to find on FDA website.
In 2008 there where 5,962 open commercial INDs at FDA. I could not find current number but I'd guess it is at least around 7,000 now. In past 7 years, there have been average of 600-700 new commercial INDs filed each year, 648 in FY2011 and 208 so far in first 3 months of FY2012.

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11. alig on January 21, 2013 1:23 PM writes...

Seems about right. >90% of compounds fail in clinical trials. It takes 10+ years to go through trials. So to get out 30-50 new drugs per year you would need somewhere in the 3000 - 5000 compounds in trials at anytime.

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12. Electrochemist on January 21, 2013 2:22 PM writes...

Derek's question is an interesting one. As a test, I did a quick and dirty search on "Clinical Trials dot Gov" on my lunch hour for drugs being tested in ALS. I found 56 different compounds or combos with at least 1 unique component listed (admittedly, some are not "drugs' in the conventional sense). Not too different from the n = 61 figure claimed by PhRMA.
------
Here's the list for those interested....
ALS-002158
ALS-002200
ALS-357
Anakinra
Arimoclomol
Botox
ceftriaxone
Celecoxib + Creatine + Minocycline
Cistanche Total Glycosides
CK-2017357
coenzyme Q10
Creatine and Tamoxifen
creatine monohydrate
cyclophosphamide + anti-thymocyte globulin + cyclosporine
Dexpramipexole
Dronabinol
E0302 (mecobalamin)
escitalopram
Glatiramer Acetate
granulocyte - colony stimulating factor (G-CSF) + erythropoetin (EPO)
Granulocyte Colony Stimulating Factor
GSK1223249
insulin-like growth factor-1 (IGF-I)
ISIS 333611
KNS-760704
leuprolide + testosterone
Lithium Carbonate + Riluzole
lithium carbonate
MCI-186
Memantine (Ebixa)
minocycline
Modafinil
NP001
Olanzapine
Olesoxime (TRO19622 + Riluzole)
ONO-2506PO
Ozanezumab
Pioglitazone + Tretinoin
Pyrimethamine
R(+) pramipexole dihydrochloride monohydrate
rasagiline
SB-509
sNN0029
sodium phenylbutyrate
Sodium Valproate
Somatropin
stem cells
Talampanel
tauroursodeoxycholic acid
TCH346
Thalidomide
TRO19622
Vitamin E
Xeomin
YAM80
Zinc and Copper

Permalink to Comment

13. anon96 on January 21, 2013 4:58 PM writes...

"Antisense RNA Interference (RNAi) ........... Thus far, two RNAi therapeutics have been approved, .........."

wrong and wrong; Antisense (single strand oligo) and RNAi (double strand oligo) are two different strategies but use oligonucleotides as drugs. Two oligonucleotide drugs approved so far, one is an aptamer (Pegaptanib, neither antisense nor RNAi) and another is an antisense (Fomivirsen, discontnued due to no market/patients). No RNAi oligonucleotide drug has been approved yet!

Permalink to Comment

14. Anonymous on January 21, 2013 5:03 PM writes...

@ Electrochemist,

Your list looks like that for AD drugs (my field). Some mystery compounds, a few maybes, but mostly a lot of compounds where the underlying scientific rationale is quite dubious indeed.

Maybe others could comment on how people manage to get funding for so many expensive and unlikely clinical trials...

Permalink to Comment

15. petros on January 21, 2013 5:15 PM writes...

The figures look on the high side to me. The databases often don't distinguish well between phase and indication, and are also slow at picking up (or recognising) discontinued compounds.

135 in phase III for infectious disease is surely almost all antivirals. The antibiotic landscape is heavily depressed as highlighted by multiple meetings in recent years

Permalink to Comment

16. gippgig on January 21, 2013 6:53 PM writes...

If there are over 4500 drug companies I'd expect more than 5000 drugs under development.

Permalink to Comment

17. anon34554 on January 21, 2013 11:41 PM writes...

I see your point about the figure seeming high. I guess the question is high relative to what? It's certainly the case, as you point out, that all the PI3K inhibitors are counted as potentially first in class. Once one of them crosses the finish line that number will drop to exactly 1 that ended up being first in class. So in that sense the number is high -- as only one per class can be first. However, it seems interesting that 70% of the activity is directed toward things like PI3K inhibitors -- even if there are several in development being counted -- rather than another statin, or SSRI.

I think that all this implies is that there are clusters of activity at multiple companies around some exciting target. This seems just as true in products in development phase as in basic science research. Clusters of papers around a new mechanisms.

You can see this at Roche/Genentech. They have two independent R&D arms that report up into Roche and I've heard executives say that researchers might be pursuing the same targets in both R&D arms, yet they don't try to combine/eliminate this duplication as it is unclear where the discovery will come from.

Permalink to Comment

18. Oligodendrocyte Expert on January 22, 2013 4:35 AM writes...

Regarding the ALS compound list posted by Electrochemist: dexpramipexole and KNS-760704 are actually one and the same (so 55 ALS cmpds., at best, not 56). Biogen licensed this compound--which unfortunately just failed in a Phase III ALS trial--from Knopp Biosciences.

Permalink to Comment

19. mr. fixit on January 22, 2013 8:57 AM writes...

Hey all, I know this is the internet and everyone gets to be cranky without restitution, but really??? Derek may have made some very minor grammatical mistakes in a few of the blog posts, but I think we should all thank him for the posts, and the conversations they create rather than making a federal case about italics.

Thanks Derek

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20. IPO Flipper on January 22, 2013 9:12 AM writes...

Ha Ha, thus the real reason for the collapse of this industry, business types focused on smoke and mirror shows.

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21. Ian on January 24, 2013 11:06 AM writes...

I was most interested to read both the PhRMA-backed report and Derek’s thoughts on it. I’m Senior Director at Citeline for the pipeline database Pharmaprojects/Pipeline, and we have been publishing similar types of reports for upwards of twenty years. We actually have two based on more recent data than that cited in the report; one from May 2012 which can be accessed at http://www.citeline.com/resource-center/whitepapers/ and another due to be published any day now. In both, our numbers are somewhat lower. Specifically, the Jan 2013 data will show that we report 1,446 compounds with a global development status of Phase I, 1,889 at Phase II, and 693 at Phase III. [In our figures too, drugs are not being double-counted across multiple indications.] We consider ourselves to be extremely rigorous in weeding out the so-called ‘zombie compounds’ – those which we believe to have fallen out of development, even though they might still be listed on company web sites – which might account for our lower figures.

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