Over the last two years there has been an encouraging spike in the rate of new drug approvals at the FDA, a boost for an industry that devotes tens of billions of dollars a year to drug research. But Bernard Munos, one of the sharpest critics of the drug development industry, takes Big Pharma to task once again on the innovation front after reviewing just what's been approved over the past 12 years.
A total of 353 new molecular entities were approved from 2000 to 2012, Munos writes in Nature. About two thirds of those approvals were for small molecules, with close to half falling in one of three disease categories: cancer, infectious diseases and CNS. Out of that batch, 324 NMEs had known modes of action targeting 190 mechanisms; 1.7 drugs per mechanism. And out of all the mechanisms a bit more than half--98--were novel. Those novel mechanisms were targeted by 125 drugs.
"Some mechanisms, like tyrosine kinase inhibitors, were used by multiple first-in-class drugs because of the unique binding patterns of many multikinase inhibitors," Munos notes. "Others, like antiretroviral entry inhibitors, targeted different proteins involved in the HIV entry process, resulting also in multiple first-in-class drugs for this mechanism."
A total of 29 of the 98 first-in-class therapies were succeeded by a follow-on drug using the same mechanism, with a median time between the original and the follow-up at two years, in keeping with earlier research on this narrowing trend. It also squares with Munos' notion that the "fast follower" theory--quickly ramping up a follow-up drug to capitalize on the market being carved out by the original--doesn't work very well. And besides that, the top 12 pharma companies only obtained a minority of the NME approvals.
Munos concludes that "there does not seem to be enough mechanisms able to yield multiple drugs, to support an industry. The drug hunter's freedom to roam, and find innovative translational opportunities wherever they may lie is an essential part of success in drug research. This may help explain the disappointing performance of the programmatic approaches to drug R&D that have swept much of the industry in the last 15 years. It has important managerial implications because, if innovation cannot be ordained, pharmaceutical companies need an adaptive--not directive--business model. They must be agile and able to retool themselves on an on-going basis in order to market the innovation from their R&D divisions, that may not be aligned with their core marketing franchises."
"But if innovation cannot be ordained," responded Derek Lowe in his In The Pipeline blog, "why does a company need lots of people in high positions to ordain it, each with his or her own weekly meeting and online presentations database for all the PowerPoint slides? It's a head-scratcher of a problem, isn't it?"
Isn't it?
- get the report from Munos
- here's the take by Derek Lowe
Special Reports: FDA Approvals of 2012 | Bernard Munos - The 25 most influential people in biopharma today - 2012