Precision Medicine: What Is It And Why Now?
By Koustubh Ranade, Vice President, Research and Development, MedImmune
Nearly two decades ago, the promise of precision medicine began making its mark on the pages of medical journals – along with speculation that “therapy with the right drug at the right dose in the right patient” – would define the future of medical treatment. In 2015, that concept garnered not only national prominence but federal funding after the Precision Medicine Initiative was announced.
“You can match a blood transfusion to a blood type – that was an important discovery,” then President Obama said at the time. “What if matching a cancer cure to our genetic code was just as easy, just as standard?”
The question embraced what the scientific community has long understood to be the right next step for patients facing life threatening illness, and where – with the right focus – the most exciting strides may soon be seen.
In part, this movement began with the growing understanding that trial-and-error approaches to the treatment of disease aren’t ideal. These tactics are expensive, they take time – precious time when facing potentially fatal conditions like cancer – they’re inconvenient and often unpleasant for patients, and they are inherently unpredictable. What’s more, these diseases that we study – cancer and inflammatory conditions such as asthma, for example – are complex. There are no easy answers and no silver bullets.
What we do have today, however, is the convergence of remarkable technological improvements in multiple fields that makes the timing right for a more intense focus on precision medicine. Included among these are the expanding sophistication of data science and wearables, a broader adoption of electronic health records, more engaged patients who are participating in health research, decreasing costs of genomic analyses and – from the more specific perspective of scientists and researchers – a growing understanding of the molecular heterogeneity underlying most common diseases.
With more than seven billion people in the world, this can’t be understated. While there may be similar signs and symptoms among groups of patients with diseases like asthma or cancer that make their illness superficially the same, there are underlying and inimitable molecular differences – at the genomic (DNA and RNA) and protein level.
This is both the opportunity and the challenge we now face: distinguishing individual patients at the genomic or protein level, even though they share similar signs and symptoms of disease, and then translating that molecular understanding into new precision medicines that are tailored to a patient’s illness. As our appreciation of molecular features that differentiate one patient from the next has grown, we’ve seen the shift from the traditional “one-size-fits-all” therapeutics and a trial-and-error approach to precision medicine. Together with such precision medicines comes the requirement for new diagnostic tests – companion diagnostics – that will enable us to target the right patients.
New, investigational targeted molecules
In my work at MedImmune, we’ve focused on this area for quite some time, particularly in our core therapeutic areas that include oncology and respiratory, inflammation, and autoimmunity. Recently, our research site in California held its inaugural translational science forum to talk about the many advances we’ve seen in precision medicine in just the past few years.
We’ve learned much about these conditions. With lupus, for example, we know that inflammatory signaling in the body by cytokines plays a role in its pathogenesis, and that elevated levels of type 1 interferons – types of signaling cytokine – correlates with more severe disease activity. With asthma – comprised of several distinct patient subsets driven by different underlying disease biology—there is now strong data that implicate at least two different key cytokines and cells types: interleukin-5 (IL-5) and eosinophils and interleukin-13 (IL-13) via impact on multiple cell types. This knowledge informed our development and study designs for benralizumab, tralokinumab, and anifrolumab.
The key for each of these molecules and others in development has been our ability to understand the molecular pathways responsible for the types of symptoms these patients have; to translate this understanding into better hypotheses for drug targets; and then to identify which patients will benefit the most. We need to get each of these steps just right to successfully develop new precision medicines.
Cancer at the vanguard
Precision medicine also drives cancer drug development efforts because of the number of genetic mutations that medicines can target. And, it’s an area that has benefited significantly from a proliferation of work characterizing the genomes of thousands of patient cases that span nearly all major cancer types, as has been discussed in multiple peer-reviewed journals over the last few years. The Precision Medicine Initiative has allocated a $70 million funding increase in oncology alone, because it is clear that cancer sits at the vanguard of precision medicine.
An early example of precision medicine in lung cancer is the development of medicines like Epidermal Growth Factor Receptor tyrosine kinase inhibitors (EGFR-TKIs) that target a subset of lung cancer patients with tumors that have mutations in EGFR, making tumors dependent for their survival on the growth signal from this pathway. A more recent example is the development of another precision medicine, for patients whose tumors become resistant to medicines like an EGFR-TKI because of a second mutation in EGFR.
Despite its swift evolution, promise and recent recognition, precision medicine remains far from mainstream. The scientific community is essentially at the bottom of the mountain looking upward and outward toward a landscape of immense potential. Among our hopes is to uncover a handful of dominant molecular pathways to further focus our research, and then use expanding and evolving technologies – including combination-focused programs and companion diagnostics—to translate those efforts into life-saving medicines for patients.
About the author
Koustubh Ranade is Vice President, Translational Medicine at MedImmune with responsibility for developing biomarkers and companion diagnostics for oncology, respiratory, inflammatory and autoimmune diseases. His group has discovered and is developing novel predictive biomarkers as companion diagnostics for therapeutics in development for immuno-oncology, severe asthma, atopic dermatitis, Crohn’s, rheumatoid arthritis and lupus. Prior to MedImmune, he was at Genentech and Bristol-Myers Squibb. He has published extensively on human genetics and pharmacogenomics; co-authored and edited a book on the application of genomics to drug development, and is an inventor on four issued patents. Koustubh received his PhD from the University of Massachusetts Medical School, and did postdoctoral work at the National Human Genome Research Institute of the NIH and at the Stanford University School of Medicine.