Sponsored Insight
On my first day of medical school we were handed an essay written in 1927 by American physician Francis Weld Peabody entitled ‘The Care of the Patient’.[1] Despite being written 95 years ago it remains fresh today. While we think that the rapid pace of advances in science and medicine is a recent phenomenon, Peabody writes of “…the amazing progress of science in its relation to medicine during the last 30 years, and the enormous mass of scientific material which must be made available to the modern physician.”
Peabody’s point is that to address human suffering we need to combine scientific information with dedication to understanding the patient experience. “Disease in man is never exactly the same as disease in an experimental animal,” he writes, concluding “…one of the essential qualities of the clinician is interest in humanity, for the secret of the care of the patient is in caring for the patient.”
Over my eight years as chief scientific officer at Vertex Pharmaceuticals I return to Peabody’s essay – and my own days as a practicing physician – to identify and prioritize opportunities to bring transformative new medicines to patients. Strategy and prioritization are key because (a) a vast array of new opportunities emerges each year from academic laboratories, (b) the high cost and years required to test each one for potential benefits to patients, and (c) success discovering breakthrough medicines is rare.
At Vertex we believe the greatest value for patients and society is to discover and develop transformative medicines that address the underlying cause of serious diseases. To achieve this goal we invest >70% of our operating expenses in R&D. For this corporate strategy to succeed, our R&D strategy needs to provide rates of success higher than the industry norm.
The Vertex R&D strategy to discover and develop new medicines
There are at least four reasons it is challenging to discover and develop first-in-class medicines. First, knowledge of causal human biology remains limited. Second, even where we gain understanding of the underlying cause of a human disease, there is seldom an established therapeutic modality to address it. Third, it is challenging to predict the profile of a new medicine until it is tested in patients. Fourth, it takes a decade or more to test each new hypothesis, and only 5% of clinical candidates ultimately make it from Phase 1 to approval, with the steepest cut at Phase 2 due to failure to achieve proof-of-concept.[2],[3],[4]
In 2015 we developed a new R&D strategy to increase the chances of success discovering and developing breakthrough medicines. First, we work only on targets that have been validated in humans as playing a causal role in human disease. Second, rather than be limited by one modality, we embrace therapeutic innovation beyond our traditional strength in small molecules. Third, we choose programs where there exist or we can invent highly predictive in vitro assays based on primary human cells, and early biomarkers that predict long-term success. Finally, we select opportunities where the clinical and regulatory path enables efficient assessment of therapeutic potential and to potential approval. (More detail on this R&D strategy can be found here.)[5]
We select programs that address serious diseases with great unmet need, addressing targets proven to play a causal role in human disease with innovative modalities. Both in our own labs and through partnerships we aim to “crack the biology” of each such disease – that is, identifying a new therapeutic approach with transformative potential. Once we obtain such evidence in a translational assay we ‘pour on the chemistry’ to rapidly discover and develop multiple clinical candidates. We choose to test multiple candidates in early development because, while our strategy increases the likelihood of translational success, the properties of a candidate medicine ultimately determine its clinical profile – that is, potency, specificity, drug-like properties, exposure, metabolism, stability, manufacturability and, of course, safety and tolerability. Where practical we advance multiple candidates into the clinic to characterize each potential medicine’s profile in patients and only advance the best to pivotal development.
How has the strategy performed?
Over the period from 2011 to 2019 Vertex launched five medicines discovered in our own laboratories. Only a handful of companies founded since the advent of the biotechnology industry have a similar track record. And yet, the hardest thing in our industry has been to do it again – to serially innovate across multiple serious diseases.
In recent years we brought forward clinical candidates in six new diseases based on this R&D strategy. Each represents a first-in-class mechanism of action, each with an innovative approach. Five of the six are now past proof-of-concept, and the sixth achieved proof-of-mechanism in patients. While there is much to be done, these clinical data indicate progress in our goal of improving the rates of success translating novel human biology into patient benefit.
At Vertex, progress of pipeline motivates us, but it is a weighty responsibility. Our goal first and foremost is to benefit patients and families living with serious disease. Following Peabody’s guidance, we continue to focus on the patient as we relentlessly execute our disciplined strategy to improve the health of communities in which we live. Learn more about our science here.
References
[1] Peabody, F.W. The care of the patient. JAMA 88, 877-882 (1927).
[2] Bunnage, M.E. Getting pharmaceutical R&D back on target. Nat Chem Biol 7, 335-339 (2011).
[3] Thomas, D.W., Burns, J., Audette, J., Carroll, A., Dow-Hygelund, C., Hay, M. Clinical development success rates 2006-2015. Biotechnology Innovation Organization, Biomedtracker & Amplion (2016). Available at: https://bit.ly/3ItQpgl. Accessed February 21, 2023.
[4] Plenge, R.M., Scolnick, E.M., Altshuler, D. Validating therapeutic targets through human genetics. Nat Rev Drug Discov 12, 581-594 (2013).