Besides the cloudy economic picture in the established pharmaceutical markets, much of the current cost-cutting in pharmaceutical R&D can be explained by a loss of confidence of the industry in their own ability to efficiently develop drugs. This assessment is largely made by MBAs without a biomedical background who will measure current industry productivity in terms of how many drugs get approved today, that is 10-15 years after most of the critical development decisions were made. Worse still, instead of considering the new biotechnologies and exponentially growing insights into human biology and disease as a solution, because the downturn in productivity seems to be correlated with the genomic revolution, of which RNAi has become an indispensable part, these very technologies are blamed for increasing the cost of drug development. If you thought Luddites were a phenomenon of the 19th century, think again.
In this context, I found it quite refreshing to listen to a presentation by the Vice President of Research & Early Development at Genentech at the Stanford ‘DFJ Entrepreneurial Thought Leaders’ seminar series (highly recommended, podcast available on iTunes) in which Richard Scheller predicted that industry productivity is going to improve significantly (note: while Roche owns all of Genentech, Genentech’s R&D remains separate). In his opinion, one of the main reasons for the industry’s poor record these days of getting drugs past the regulatory agencies was a spending glut when biology wasn't ripe for it. In the 90's, right along with the internet bubble, there was a strong belief that the pharmaceutical industry was invincible. When the harvests from the small molecule revolution were aplenty, companies offered their R&D heads quite a bit of the profits for re-investment. Needless to say, these VPs did not hesitate one moment, accepted and spent it. Unfortunately, 'pre-genome era', there were not that many well validated targets and projects to spend that money on and that’s how we end up with the $1-1.5B figure popularly cited for what it takes to get a new drug approved- on average.
This, however, has changed dramatically according to Dr Scheller due to the information explosion brought about by the new biotechnologies (high throughput sequencing, RNAi, proteomics etc). As a result, we have now many more validated targets to choose from. This, he predicts, will be a major force in re-invigorating industry productivity.
It is the ability of RNAi Therapeutics to pretty much go after any drug target, and often not just one but a few in parallel (see Alnylam’s VSP or Tekmira’s Ebola programs), that should make it so valuable to the industry (my thoughts).
Richard Scheller then added that not all Big Pharma companies will participate in reaping the benefits of these advances. Without naming names, he said that some companies have 'lost their way' and will pay for neglecting R&D. Cutting internal R&D and out-sourcing the rest will cause these companies to lack the expertise to make the right technical go/no-go decisions. While commercialization is clearly important at the end of the process, he warned that commercial considerations are often brought into play too early in the process and he cited some examples in which products with mediocre sales forecasts became Genentech’s biggest sellers and vice versa.
I guess John Maraganore referred to this as ‘hyperanalytical insanity’ in a 2009 interview with Xconomy. It also reminds me of comments by Art Krieg, then head of Pfizer’s RNAi Therapeutics efforts, which doubted the commercial potential of drugs that are intravenously administered. If a translational medicine person credited as a father of TLR therapeutics starts to think along these lines, you get an impression of the brain-washing powers of sitting in the boardrooms of Big Pharma.
Intravenously administered RNAi Therapeutics for the treatment of hypercholesterolemia is probably a good example of such mis-placed early criticism. Critics say that with such a mode of administration alone, this can never be a big seller in the lipoprotein-modulating market. This, of course, entirely neglects the high unmet need of the millions of patients not well served by currently available medications alone. It also is not open to the possibility that the eventual clinical profile will be so differentiated and/or superior/complementary to existing approaches that patients and doctors are quite happy to accept infusions every month or two. Without testing it at least in phase II studies, nobody really knows what the commercial profile will be.
To most of the readers here, Richard Scheller probably stated the obvious. Nevertheless, it is good to hear somebody influential in the industry still apply logic to drug development at a time that RNAi Therapeutics has become such a popular punching ball. These pockets of reason within Big Pharma/Biotech will be critical in keeping RNAi Therapeutics move forward for everybody’s benefit.