Darwin's theory of evolution is a framework by which we understand the diversity of life on Earth. But there is no equation sitting there in Darwin's 'Origin of Species' that you apply and say, 'What is this species going to look like in 100 years or 1,000 years?' Biology isn't there yet with that kind of predictive precision.--Neil deGrasse Tyson
In the last 6 months to a year I have been working almost exclusively in the immuno-oncology space. Either directly with industry, on a collaborative team, or as a numeracy expert helping physician groups and/or patient advocacy groups unpack the latest findings.
After attending the World Vaccine Congress, Immunology 2017, DIA/FDA Statistics Forum, and Duke-Margolis Center for Health Policy/FDA workshop on analytical validation of assays used in qualifications of biomarkers I can tell you the headlines announcing potential cures and breakthrough approvals for checkpoint inhibitors are misleading and superficial in their conveyed messages.
Here is a simplistic representation of immunotherapy to introduce you to the basic premise in case this isn't an area of expertise.
What if we approved drugs based on the biochemistry. Similar to Eureresist what if drugs were classified based on their ability to increase trafficking and penetration of tumor by T cells, T cell activation, and quantity of tumor-specific T cells for example. We can look at the graphic and see the myriad of options. What may result is the combination of HIV style cocktails that tailor treatment to the specific biochemistry of the tumor AND the patient. In the absence of clunky monotherapy or combination therapies we don't truly understand--we now have measurable endpoints beyond overall survival, progression free survival, etc.
The most-effective to date has been PD-L1 expression but we shouldn't be convinced of a simplistic one biomarker gateway. An article published in 2016 by Manson and colleagues Biomarkers associated with checkpoint inhibitors highlight biomarkers with the potential to predict efficacy and toxicity.
Inherent in the measurement of biomarkers, unlike the measurement of xenobiotics (drugs), is that biomarkers are endogenous entities or molecules. Therefore, biomarker assays typically measure an increase or decrease in the endogenous level of the molecule which often fluctuates because of individual variability in physiology, disease biology, pathology, comorbidities, treatment administered, and environmental factors. Given these factors, the requirements and expectations for assays used in the qualification of biomarkers must take into consideration 1) the type of molecules being measured and 2) the context in which the biomarker is being applied in drug development and in regulatory decision-making.--Public Workshop Duke Margolis Center for Health Policy, DC