Developing new medicines is an amazingly difficult undertaking. The research portion alone is daunting, and for those of us who have actually attempted it, humbling. A recent article reminded me just how little many people understand about the drug discovery process. The basic premise of “Pharma Needs an Innovation Intervention” was that pharma should change its focus from “finding druggable targets” to “deliver a consumer-focused product and service and a business model that goes beyond the product itself.”
Unfortunately, the article doesn’t address two critical issues; one grounded in the past, the other the future. First off, why has Big Pharma, after being one of the most profitable industries for decades, suddenly become so remarkably unproductive in coming up with new medicines? Second, if Big Pharma walked away from the difficult task of “finding druggable targets,” then who would take over the job of creating new medicines? From a business point of view, one can see a clear need to alter a revenue model that may not be working for Big Pharma any longer. However, from a practical and societal perspective, there needs to be some way of innovating new medicines, not just new business models.
I wish I could provide a definitive reason why Big Pharma, as a group, has become so unproductive in recent years. These companies are not monolithic and have distinct styles for running their businesses. To paraphrase Tolstoy’s Anna Karenina “Productive drug companies are all alike; every unproductive drug company is unproductive in its own way.” It’s easy to congregate a lineup of the usual non-productivity suspects: excessive layers of bureaucracy, fear of making the wrong (or any) decisions, entrenched industrial group-thinking, failure to recognize and support an innovative culture, and new regulatory uncertainties. I suspect that all of these concerns contribute to the productivity problem, but it’s difficult to quantitate exactly how important each of these factors really is.
I think Big Pharma is still hung over after a difficult transition from a decades-long focus on screening chemical libraries to more of a recombinant DNA/genomic biology mindset. It may very well be that after a century or so of effort, all of the “low hanging fruit” really has been picked off of the medicinal tree. Finally, consider that Big Pharma’s recent attention was focused on developing blockbuster drugs that would bring in sufficient revenues to feed their bloated organizations. Genzyme’s marked success in treating rare diseases (along with its recent acquisition by Sanofi) illustrates how that thinking has changed.
So why is coming up with new drugs so difficult? The answer is actually pretty straightforward: because biology is amazingly complex. It’s not rocket science; it’s much harder. With all due respect to the people that design and build our space vehicles, uncovering the functional role of thousands of unique biological molecules is a significantly more complicated undertaking. Twelve years is about the average length of time it takes for a single drug to be discovered, developed, tested, and approved by the FDA. Twelve years also defines the time period between the start of the space age (the launch of Sputnik 1 in 1957) and humans landing on the moon in 1969.
Even more difficult than figuring out the function of biological molecules is coming up with a way to alter, in an appropriate way, the divergent activities of selected subsets of these molecules to treat various diseases. People can be afflicted with literally thousands of different ailments. As living organisms, we reflect eons of genetic diversification and are vulnerable to rogue viruses, bacteria, fungi, and environmental pollutants. No two of us are alike, not even identical twins. People also suffer from pain, are susceptible to psychological disorders including addictions, and are at risk of unintentional side effects brought on by numerous medications. The biological and rocket sciences do share one primary characteristic: they are both very expensive, high cost-of-entry businesses.
