Has biopharma over-invested in cancer R&D?

Since joining the Novartis Institutes for BioMedical Research (NIBR) two years ago, I have faced this question many times and in many settings. I must admit responding almost reflexively and dismissively at first – how 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 immuno-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 or 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”. 

No. The burden of cancer remains massive and pernicious – for affected individuals, for families, for healthcare systems, even often for survivors. I regard the estimated $50 billion annual investment in cancer as fully era-appropriate. Never before have we better understood the environmental, genetic and epigenomic causes of cancer; and never before have we been better equipped to respond with imaginative and effective therapeutic modalities. As a career cancer researcher and cancer doctor, I feel the shifting of the tide. Historically intractable targets are nearly in reach, the power of the immune system holds promise against the perilous mutability of the tumor genome, and we are starting to take notice of pre-emptive therapeutic strategies. Against the global burden of these impossible diseases, we could justify twice the present investment.

But our community has invested wrongly. The cutting edge of cancer research is moving quickly, creating a wave of innovation in its wake. Our work with the University of Pennsylvania to create first CART therapies for cancer is surely just Chapter 1 of an evolving, important work of non-fiction. The narrative today is rightly co-authored with innovators around the world. There is so much important work remaining – extending impact to solid tumors, simplifying manufacturing, establishing definitive combination approaches, marching up towards early-disease therapy, solving challenges inherent to allogeneic platforms, and engineering regulatory control over these living therapies. But the denominator of CD19 CART research is massive, and not always differentiated. The flood of redundant checkpoint agents is equally jarring. 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 too high for patients to bear.

We must organize tough targets, always reaching for the highest-hanging fruit: a nuanced insight into synthetic lethality, a new path to intractable protein targets, first selective inhibitors of oncogene-encoding RNA. We must pursue medicines with curative intent, and develop new agents towards survival benefit – invariably in mechanism-based combinations as they will be used in practice. We must recommit to pre-emptive therapies, that respond to circulating tumor DNA long in advance of the radiographic shadows and threatening symptoms that threaten and take the lives of patients. And we must think – and work – outside the box, inviting any and all with creative solutions to join in this historic battle against a longstanding enemy. 

At the Novartis Institutes for BioMedical Research, we have reconfigured our cancer discovery efforts around these principles, prioritizing first-in-class and well differentiated agents and anticipating the definitive use to maximize patient benefit. Regrettably, there is an intermediate strategy for many well-resourced discovery units, particularly in biotech. Astronomical sales of promising technologies to pipeline-poor pharma giants creates a profitable market for impact promised but not yet realized. At Novartis, we have no intermediate strategy. There is only impact. 

But we cannot do this work alone, in private isolation. The experience of innovating CART therapy with Carl June, Stephan Grupp and friends at the University of Pennsylvania powerfully reminds that our best work is often done shoulder-to-shoulder with innovators beyond our walls. We recently announced a new alliance that builds on our longstanding collaboration with Harvard, focused now on combination cancer immunotherapy delivered with biomaterial systems from the Wyss Institute for Biologically Inspired Engineering. While early-stage, this technology sits firmly in our power alley of next-gen immune strategies, joining 19 clinical-stage IO assets, alongside more than 20 combination IO approaches in clinical trials. Already, our work with innovators at UC-Berkeley on chemoproteomics has identified handles for ligands to undruggable proteins. And early experience collaborating with Science37 has brought us to think not about how to bring patients to enroll in our clinical trials, but how to bring trials to patients. 

Our community is not over-invested in cancer medicine, but it is often invested wrongly. These are gut-check moments, for both biotech companies pressured for near-term exits by impatient investors and large companies with established R&D efforts. But I see only a confluence of interests, between patients, doctors, innovators, payers and investors alike: definitive medicines for these life-threatening diseases.

Now with all that said, I’d welcome a chance to hear from any of you that are pursuing these or other follow-on strategies. Feel free also to learn more about our work in cancer research here, on our website. Okay, if you’ll excuse me I’m going to hop off this soap box and get back to digging around in a KRAS pymol session...