Jay Bradner is the president of Novartis’ Institutes for BioMedical Research, the organization entrusted with Novartis’ R&D budget of $9 billion -- one of the largest in the industry. Furthermore, Novartis is a leading innovator in the oncology field with targeted therapies as well as the recently launched CAR-T therapy Kymriah for a deadly childhood leukemia. Given his important, influential role in the future of oncology research, one can’t ignore the question he asked in a self-described “soapbox moment”: “Can we as a society be over-invested in working to cure cancer?”
This is a time of extraordinary promise for cancer medicine, with unambiguous evidence of progress in the innovation of both targeted and immune-oncology therapies. And the first blush of activity in advanced disease from new agents is so hopeful, rightly prompting a redoubling of effort to identify additional and partner therapies responsive to mechanisms of intrinsic and acquired resistance. But witnessing the flood of fast followers, narrow differentiators and distracting hype, I must admit it’s starting to sound like a very reasonable question.
My answer is ‘no, but".
Bradner admits that “there is so much important work remaining” but bemoans the massive amount of work in areas like CD 19 CART research and the “jarring” flood of redundant checkpoint agents.
I am inclined to believe that a positive storyline underlies fast-follower research – enthusiasm, passion or an overlooked indication. But I do fear that the commodity market for active cancer drugs that exists today in big pharma has inadvertently fueled redundant investment in the biotech sector, with an opportunity cost to society for patients to bear.
My answer to Bradner is “Yes, but”.
Historically, the biopharma industry has often piled into areas where confidence was high, but which ended in disappointment. Years ago as many as 20 inhibitors of platelet activating factor (PAF) were put into clinical trials in an attempt to come up with a breakthrough for respiratory diseases -- all for naught. There was a stampede to find inhibitors of substance P (neurokinin 1) which was thought to play a role in depression, pain, asthma, migraine, etc., but all of this research only yielded Merck’s antiemetic, Emend. However, sometimes focus in areas turns out to be important, as happened with the statins. While initial R&D yielded important drugs like Merck’s Zocor and BMY’s Pravachol, so-called “fast-followers” Lipitor (Pfizer) and Crestor (AstraZeneca) proved to be superior. It is also likely that the initial wave of targeted cancer therapeutics will be eventually replaced by agents with improved efficacy and less resistance. In reality, rarely does the first agent of a class turn out to be optimal. In addition, no single drug works identically across diverse patient populations – young/old, male/female, different races, etc. It’s important for patients to have choices.
Ultimately, patients, payers and physicians will gain a great deal by this perceived overabundance of oncology R&D. As Bradner says, this is a time of extraordinary promise, a time when a cancer diagnosis is not necessarily a death sentence. This is becoming a disease that can be treated – and maybe even cured – with a combination of novel drugs, converting cancer into a chronic disease. Soon, we will have improvements on current drugs that are expensive and which only extend lives by a matter of months. Furthermore, research now underway will help to identify drug combinations that will work best for specific cancer types – not a simple task and one that is requiring a lot of R&D investment.
Yes, productive research will lead to a number of competitive agents – some in the same therapeutic category. But, competition will not just allow for better agents to be found, but also result in price competition that will drive down the cost of these medicines. It is interesting to note that Bradner’s boss, Novartis CEO Vas Narasimhan, has publicly made the case for second generation oncology assets which will meet a rising set of standards needed to benefit patients. The rising bar for new drugs can only benefit cancer patients.
The real pressure caused by the presumed overabundance of cancer research falls on investors and decision makers who guide R&D portfolios. The decision to invest in new cancer programs is based on a number of factors. How novel is the approach? How likely will it yield a drug which is a significant improvement on current and future therapy? Does it complement our cancer portfolio? Where does this program stand with respect to the competition? At the end of the day, R&D investments always involve a high degree of risk and each company needs to try to invest as wisely as possible. But, ultimately, patients are the ones who benefit most from the extraordinary era of research that we are now presented with. Let’s capitalize on it.
