Labcorp Drug Development has continued to invest in the technology, capacity and expertise globally to support the evolving and complex analytical needs of our clients. We recently spoke with Katherine T Landschulz, PhD, Sr. Director and Lead Scientist, Cardiovascular and Metabolic Disease, Neurodegeneration at Labcorp Drug Development, to learn about the power of emerging biomarkers and new opportunities for precision medicine approaches in kidney disease.
Tell us about the current biomarker landscape for kidney disease.
Renal disease is such a fascinating area. There are some tremendous advancements in new medicines that have just come on the scene in the last 2- 3 years which have truly been game-changing. Chronic kidney disease, for example, affects millions of individuals in the United States and across the globe, with historically very few treatment options. Recent drugs demonstrating benefit for kidney disease patients include an interesting new selective mineralocorticoid receptor antagonist and multiple sodium glucose co-transporter inhibitors (SGLTi). While kidney disease biomarker discovery efforts have been ongoing and extensive, it is with the advent of these new drug approvals that we see accelerated focus and energy in the development of biomarkers for kidney patient care. So all those classes of biomarkers that we like to think about: early detection, diagnosis, prognosis, monitoring-come into play as being even more necessary when you have medicines which are now clearly showing an impact in disease intervention.
Compared with other therapeutic areas what are the challenges in the development of new biomarkers for kidney disease?
I think about both “quantity” and “quality” challenges in kidney biomarker disease development. By quantity, I mean getting better, wider uptake of basic testing, including Urinary Albumin Creatinine Ratio (UACR), and estimated Glomerular Filtration Rate (eGFR). These are needed to form a foundational understanding of an individual’s renal disease status. But, secondly, there is a quality gap, in that there is a need for more biomarkers that detect disease earlier and more specifically. We would like to be able to differentiate sub-groups of patient from each other in order to identify which patients are most likely to positively respond to particular therapeutic options.
We are looking at both of these challenges very carefully. When we look at data reflecting patterns of patient care, we can see that the majority of patients, who would otherwise be indicated as being at risk of kidney disease, are not being tested for UACR and eGFR. This is particularly evident in regions of the US, for example, for which the population at large is medically underserved. Meanwhile, there is a lot of work being done on interesting biomarkers that show promise for earlier detection as well as disease monitoring, including those supporting precision medicine type of approaches for additional new medicines.
So, here, unlike in other diseases, we actually have relatively accessible and low-cost tests available for basic monitoring kidney disease in primary care setting. It’s extremely important for overall health and huge for quality of life that folks are get tested early enough. We need physicians and patients to recognize the need for testing in kidney disease. This remains a major area for education. Increased uptake of basic testing will enable the development and uptake of better-more precise and more accurate-kidney disease biomarkers.
What is the potential for precision medicine in the area of kidney disease?
Precision medicine approaches to kidney disease are very exciting. This is the concept of being able to have a new medicine that is truly targeted to the right patient the right dose and having it accompanying that new medicine with a very specific test, or series of tests that truly identify the patient who’s going to benefit the most. There’s been some very interesting work done from a precision medicine standpoint with a condition called focal segmental glomerular sclerosis (FSGS), FSGS is a rare disease that is significantly more prevalent in individuals of African compared to those of European descent. Research has identified the presence of a genetic variant in a gene called APOL1(encoding apolipoprotein L1 or apoL1) which is tightly linked to FSGS. part of our “good cholesterol” HDL particles. While direct causality of the resulting altered apoL1 and FSGS has yet to be established, there are several pharmaceutical companies who are nonetheless working on designing medicines which targeting apoL1, inhibiting its function activity. Individuals would be genetically screened to be identified, with individuals carrying 2 copies (homozygous), and potentially a single copy (heterozygous), of the disease susceptibility alleles would be considered amenable, and therefore eligible, for treatment. This is an excellent example of a precision medicine approach applied to kidney disease.
The field will be looking to learn from this for future drug development. A well-established approach has been to take a look at an extreme circumstance in a rare disease where there’s a known single genetic mutation, or perhaps a limited number of mutations, intervene with that aberrant gene product, then learn from that to investigate if your medicine might, in fact, have some interventional capabilities in a broader patient population. So we’re looking at the APOL1 activity and programs that sponsors have ongoing for FSGS to see how well those work. and then see if there may be learnings which enable identification of additional molecular contributors (genetic and beyond) which point towards new targets and approaches which will really help us move the needle for kidney disease patients.
What impact will advancements in kidney disease biomarkers have in the next several years?
What I would like to see and what many of us are hoping to see is a real sea change for kidney disease. I mentioned that there are groups of individuals out there that really were not being effectively reached with testing. We’re hoping that with more awareness, that that will change very significantly. There are also some really interesting advances that are going on in the realm of looking at what can be done in a decentralized way, such that at-home collection and/ point of care testing devices can enable the testing needed to be performed at home without having to come into a hospital setting. We are also seeing the emergence of new, digital device test-based resulting capabilities for kidney disease patients. There are several different devices in development out there which look very, very promising. With these advances, we are hoping that we can start to shift increased patient awareness piece back to true patient empowerment. Everybody probably knows somebody who undergoes dialysis and knows what a tremendous impact that is on quality of life. If we can shift awareness via biomarkers such that people get diagnosed early, get the medical intervention they need, and are monitored for effective response and outcomes, we will hopefully be able to avoid or at least significantly postpose dialysis. So, that is what I think I’m most excited about for renal disease in the future and biomarkers.