ChEMBL

Protein kinases are one of the 'hot' families in drug discovery, and last year (2011) had the highest number of approvals for protein kinase inhibitors ever - 4, these being Vandetanib (Zactima), Crizotinib (Xalkori), Ruxolitinib (Jafaki) and Vemurafenib (Zelboraf). Some of these are real breakthrough medicines, offering seriously ill patients improvement of life/extended life in terminal diseases. 2011 also saw the assignment of 12 new INNs/USANs for protein kinase inhibitors - these will form the cohort of drugs from which future approvals will come. It's interesting to track the approval ratios, a comparison of input to output (numbers of INNs/USANs to the number of approvals). Of course, there are some challenges with applying a simple approach such as this, since there is a delay between USAN/INN assignment and approval, but this will probably only be a significant issue when there is a large increase/decrease in a particular year. We also know that the 'time constant' between USAN/INN assignment and approval is about 2-4 years for approved drugs, so on average, at steady state, things will balance out.

Anyway, here are some graphs of the numbers, they should make sense without further explanation. One of the reasons for writing this was that I was at a talk recently where kinase inhibitors were treated as 'blessed' during development, that is, that they suffered lower than average attrition during development - the approval ratio is converging at about 0.2 (remember this number (one in five) is roughly the fraction of phase IIb to market, certainly not overall clinical attrition). The plotted number (blue triangles with green line) is the ratio of the cumulative USAN number to the cumulative approved number for that particular year). To my eye, the data doesn't really support this 'blessed' view - so unless the time between USAN/INN assignment and approval is systematically longer for protein kinases than other drug types (and even then under a steady assignment/approval rate scenario that doesn't matter). However, based on the large jump in 2010 USAN assignment 2013-2014 should deliver a bumper crop of new kinase drugs.


Comments as always welcome in the blog comments.

A small update - some numbers...

Highest Trial Phase	Fraction with USAN
IV (launched)	1.00
III	0.97
II	0.34
I	0.07

The phase 1 include quite a few Chinese NNs (still trying to get to the bottom of the naming scheme for these), also cancer is a little odd in that there are a lot of Phase I/II combined trials, and so the ratio of Phase I to Phase II is a little unusual.