Use Kidney Genetics to Strengthen Clinical Trial Design (Sponsored)

Will Harte

Genetics is playing an increasingly important role in our understanding of chronic kidney disease, from identifying distinct patient populations to informing clinical development and potentially changing how new therapies are studied.

Dr. Ronen Schneider

And when you start sequencing those patients, a meaningful number turn out to have a genetic answer, and that answer changes what you tell them, how you treat, moving away from a one-size-fits-all to a targeted personalized approach, and what you tell their families.

Dr. Ronen Schneider

Renasight IQ is what you get when you pair every one of those results with a patient's clinical story over time.

Dr. Ronen Schneider

And the problem we were solving is that the field has defined patients by phenotype, and the same phenotype can hide very different biology.

Dr. Ronen Schneider

That's a great question. I'd say we are at the inflection point, but we haven't crossed it yet.

Dr. Ronen Schneider

And the third gap is a numbers problem. Collectively, genetic kidney disease may account for as many as one in five patients with CKD, but individually, most of these conditions are still rare, so clinical trials have a hard time finding enough of the right patients and recruitment becomes slow and expensive.

Dr. Ronen Schneider

In one rare kidney disease study, that approach supported enrollment at about three times the typical pace.

Dr. Ronen Schneider

Here's what that looks like in our data. About 35% of FSGS labeled patients have a positive genetic result. Of these, about half carried APO1 high-risk genotypes, a bit over a fifth had a COL4A variants, and the rest were spread across podocyte and other genes.

Dr. Ronen Schneider

for a developer, this matters a lot. If you enroll FSGS without knowing the mix, you're averaging across biologies.

Dr. Ronen Schneider

They had about 35% higher rate of reaching end-stage kidney disease, and their EGFR fell about 2.7 units a year versus about 1.7 in non-genetic forms.

Dr. Ronen Schneider

On natural history, a placebo arm isn't one number.

Dr. Ronen Schneider

first, stop treating genotype as an afterthought and start treating it as a design variable.

Dr. Ronen Schneider

Take a completed or ongoing study or even your screening population and ask three questions: What fraction of these patients has a genetic cause?

Dr. Ronen Schneider

And Duplex is a good illustration of what that looks like. It enrolled FSGS broadly, then genotyped its patients, and about one in five turned out to have a genetic cause.

Dr. Ronen Schneider

But this is also the opportunity: pre-specify genotype up front and use real-world data to find enough patients in each genetic group to answer the question properly.