The Road Less Taken: The Molecular Pathways
In most big pharma research labs, the starting point for drug discovery is to come up with a therapeutic area first, viz. cardiovascular, Alzheimer's, diabetes etc. Typically these therapeutic areas are themselves shortlisted based on the market potential, relevance to as large a target population as possible, company's confidence of differentiating from other drugs in the market, and the likelihood of the drug becoming a blockbuster drug, or at the very least, something which generates enough revenues to justify the investment in the entire R&D process to bring it to market (estimates indicate that the cost of bringing a new drug to market is upwards of $1 billion!)
The next step then is to try to identify a molecular entity or genetic sequence that comes close to exhibiting the various properties desired in terms of disease treatment. To do this actually requires sifting through tens of thousands of likely candidates, sometimes even more, at the very early stages of the process called discovery. That could take months and years, and cost millions of dollars. And the search may still prove futile. Even after a candidate has been thus identified, it has to pass through the grueling research process of assays and tests to determine what are the various properties and likely reactions, before it is introduced into the clinical process for actual development into a drug that can be tested and taken to market after approval. Several ifs and buts, but this is the road mostly taken by pharma companies as they seek to become more innovative in research and justify the huge investments that are required.
The road less taken is the one being pioneered by individuals like Mark C. Fishman, the Novartis research chief. He took a different tack to drug discovery and development. Rather than focus on diseases that will yield the biggest sales pop, he had his team focus on pursuing the most effective drugs without worrying about whether they treat what the market considers of substantial potential or common conditions. He concentrated on molecular pathways - which control interactions between molecules in a cell - to gain more insights into multiple ailments at one go (something that is not apparent in the beginning). And he started running trials for drugs treating diseases that afflict relatively less number of people. Once these drugs were approved and successful, he was able to use the same drug or its variant in a different disease context, due to the common molecular pathway involved.
One successful drug that came out of this approach was Afinitor, medication for patients with benign brain tumors, which was initially started as a drug to treat children with tuberculosis sclerosis, a very small and limited segment. Novartis has been able to replicate this approach in other situations as well. As John Maraganore, Alnylam chief executive, and one of their partners, says, "You might learn something about pathways in one disease setting that would allow you to use the same or related medicine for other diseases. And that makes the whole drug discovery process more targeted and more efficient."
The road less taken seems to be leading to riches for Novartis. The company has nearly 50 drugs in late-stage clinical trials, a large number even for a big pharma, and it has shown more innovation with lesser costs than its peers by doubling the number of drugs making it through early-stage trials!
To summarize the two different approaches to Research:
1. Road mostly taken - focus on the diseases with the biggest potential or prevalence, and try to narrow down the drug candidates that can treat that specific condition; high investment, uncertain results.
2. Road less taken - focus on making effective drugs for diseases that are rare, but involve molecular pathways that may control multiple diseases; parlay into success in treating other diseases, leading to more focused and cost-effective research.
Which one is your company betting on?
