Properties of Modern Drugs
So, I have a paper review to finish off, and then assess a whole pile of applications, but before that - some fun! Let's look at the general properties of 'modern' drugs, and see what general patterns emerge - for example are drugs orally dosed, what fraction are antibodies, etc. Of course, these analyses are clearly limited by small numbers, but I think they provide useful guideposts for the changing landscape of therapeutic discovery (we have a more extensive analysis of these sort of things underway) and would be happy to share ms drafts with interested parties.
The dataset I have looked at are drugs (specifically here NMEs, so novel chemical structures approved for the first time) launched in the US since Jan 1st 2007 and up until July 31st 2009 (so the past 31 months) there are 58 drugs in this set (mail me if you want some spreadsheets, etc) so not a huge number, but that's what there is. This is an average of 1.9 new drugs approved per month. Of these 58, six are not therapeutic drugs (but are imaging agents, probes, etc.), these six non-therapeutics were removed from further analysis, and all further counts refer to a therapeutic subset of 52 drugs.
Drug Class
Ten of the 52 drugs (19.2%) are proteins/peptides. Of these four are monoclonal antibodies, one is an enzyme, two are peptides, and three are recombinant proteins. The peptides can be readily accessed synthetically, and so only eight drugs (15.4%) can be considered to be biotechnology products. This leaves 42 drugs that are small molecule therapeutics.
Natural Products (and derived from Natural Products)
Of the 42 'small molecule' drugs, eight are 'natural products', defined here as either being, or very similar to, natural primary or secondary metabolites. If one considers that the peptide drugs (since they are directly related to naturally occurring molecules) are natural products as well, then 34.6% of drugs are 'Natural Product derived', however, for a more sensible definition (excluding peptides and proteins, 15.4% of drugs are 'natural products').
Dosing Route
Of the 52 therapeutic drugs, five (9.6%) are topically dosed, 18 (34.6%) are parenterally dosed, and 29 (55.8%) are orally dosed. When peptide/protein drugs are excluded from these counts, five are topically dosed, eight are parenterally dosed and 29 are orally dosed.
Black Boxes
Of the 52 therapeutic drugs, 21 (40%) had a black box warning on launch. These are equally distributed between biological (four out of ten) and small molecule (16 out of 42).
Rule-Of-Five
Of the 42 therapeutic small molecule drugs, 28 (66.7%) pass the Rule-of-Five and 14 (33.3%) fail the Rule-of-Five. It is of interest to examine the relationship between Rule-of-Five pass/fail, and oral/non-oral delivery - of the 29 Orally dosed drugs, 20 (69%) pass the rule-of-five. The data is summarised in a table below.
| Orally Dosed | Non Orally-Dosed | total | |
|---|---|---|---|
| Pass Rule-of-Five | 20 | 8 | 28 |
| Fail Rule-of-Five | 9 | 5 | 14 |
| total | 29 | 13 | 42 |
Targets
Five of the therapeutic drugs were first-in-target (9.6%), while an additional 41 have a previously 'drugged' target/established mechanism of action (MoA) and finally six (11.5%) have either an unknown, or non-targeted MoA. Of the 'newly-drugged targets for this period, four out of five have 'serum exposed' binding sites (i.e. they are secreted proteins or membrane-bound receptors), and one target is nuclear localised (but is not a human genome target).
