Strong early research is facilitating our efforts to improve our ability to predict the clinical success of our candidate drug molecules. Across the industry we are seeing strong progress using different approaches. At AstraZeneca, our early research scientists recently presented new data on how we can apply protein expression profiles in the kidney to monitor disease progression in diabetic kidney disease, offering new insights into target discovery. We are also exploring the signaling pathways involved in kidney development in collaboration with MRC Laboratory for Molecular Biology, Cambridge UK, with implications for understanding developmental kidney diseases and aberrant changes in renal cells following adult renal tubular injury.

Across the industry over the last year, we have seen a number of successful studies across chronic kidney disease as well as rare kidney diseases such as IgA nephropathy and Focal Segmental Glomerulosclerosis, which is encouraging. The treatment landscape is also evolving from looking at broad populations, to addressing specific unmet needs. For example, in our pipeline, we are looking to address persistent high proteinuria despite current standard of care, to reduce kidney function decline over time.

As a statistician, I am particularly impressed with novel design and analysis methods that give the possibility to deliver successful treatments to patients in record time. I would highlight the use of new endpoints that enable us to drive faster and leaner development programmes, such as eGFR decline over time, as well as study designs with a two-stage readout. With the multitude of new treatments available in the drug development pipelines it is important that the innovations in the study and endpoint designs continue at the same pace.

On the critical topic of novel endpoints in kidney disease trials, we have together with our collaborators at Bayer and the University of Groningen, developed a novel kidney hierarchical composite endpoint that has the potential of making kidney disease trials more efficient while still meeting the objective of slowing the progression of the kidney disease and reducing the risk of the end-stage kidney disease. We have published our research in two simultaneous papers in the Journal of the American Society of Nephrology last month. We believe that this novel endpoint, which prioritizes outcomes using clinical significance and includes broader assessment of kidney deterioration in the composite, makes this hierarchical composite endpoint an attractive alternative to the established kidney endpoints.

It goes without saying that digital technology will continue to have a massive impact, but what is key is how we prioritize solutions and scale for use. One area that is a priority for us at AstraZeneca is supporting diagnosis and we are currently doing research on a new diagnostic approach to identify patients with proteinuria using machine learning to predict ACR levels from Electronic Health Records. The model may in the future support identifying undiagnosed proteinuria and be applied in pre-screening for clinical trials. Further development of the technique may lead to a future where we can predict progression of kidney disease without needing to take a urine test at all.

What are currently the most exciting opportunities and breakthroughs in the CKD space?

The use of innovative endpoints to capture the benefits of efficacious treatments has been an important evolution and a key focus for our Biometrics team. Current successes in the kidney disease treatments landscape have created challenges for the trialists around the world, since the standard of care is rapidly evolving and the magnitude of the kidney decline over the time is lower in clinical trials. However there still is a residual risk of kidney disease progression and new treatments need to continue to be developed, and the researchers need to create innovative approaches in clinical trial designs and executions.

What are the primary obstacles confronting the CKD field that may be addressed by fostering collaborative efforts between industry, regulatory bodies, and academia during the CKD Summit?

The traditional ways of conducting kidney disease trials are becoming less feasible over time and together we need to evolve how we run clinical trials. It’s no longer just about fine tuning, it is about bringing new innovation into every aspect of clinical development; now and in the coming years.