Leadership Insights: 6thAnnual Rare & Genetic Kidney Disease Drug Development Summit

1. How would you describe the most significant shifts in the rare and genetic kidney disease landscape over the past year?

The most important shift I have seen is the move from phenotype-first to genotype-first thinking, and that is changing everything from diagnosis to trial design. Genetic testing is moving earlier in the workup, particularly in pediatric patients, where an accurate molecular diagnosis can completely reframe the treatment trajectory. Better natural history data, emerging biomarkers, stronger registries, and more constructive regulatory dialogue are making development programs more credible than they were even a few years ago. But that progress is still uneven, and for many patients it remains far more visible at specialised centres than in routine care.

2. What do you believe will define success for the next generation of renal therapeutics in terms of patient outcomes and clinical impact?

Success cannot just mean slowing eGFR decline on a population curve. It means preserving kidney function early enough that a child with CAKUT, Alport syndrome, or FSGS has a realistic chance of reaching adulthood without dialysis. It also means measuring what patients and families actually live with: symptom burden, treatment burden, functioning, and the ability to participate in school, work, and family life. Just as importantly, success should mean giving patients more options so treatment can be tailored to their individual priorities, including life participation and side effect profile. The strongest programs will be matched to the right patients, informed by biomarkers, and shaped with patients from the beginning so the endpoints, trial burden, and benefit-risk tradeoffs reflect what matters most.

3. Where do you see the biggest gap today between scientific innovation and real-world patient access in rare kidney diseases?

The biggest gap is not primarily scientific. It is structural. Patients, especially children, still go years without a genetic diagnosis because testing is not ordered, covered, or interpreted consistently at the community level. Meanwhile, science has moved much faster. We now have precision therapies in development, multi-omic tools that can stratify disease, and a much richer understanding of disease mechanisms. But none of that helps a patient in a small practice without access to genetic counseling or a speciality centre. We also need to treat clinical trials as real care options in the clinic. Many investigational therapies have the potential to be earlier-line choices with better side-effect profiles than those currently available, not simply last-ditch efforts after everything else has failed. Closing that gap requires investment in diagnostic infrastructure, education, and referral pathways well beyond tertiary centers.

4. How are advances in mechanistic biology and multi-omics reshaping target discovery in rare renal diseases such as FSGS, PKD, and Alport syndrome?

Multi-omics has fundamentally changed the questions we can ask. Instead of moving from a single variant to a presumed mechanism, we can now look at the broader molecular landscape and see how disease is actually manifesting at the tissue level. In Alport syndrome, this helps explain why patients with the same COL4A mutation may progress very differently and points toward modifier pathways that could be actionable. In FSGS, single-cell approaches are sharpening our understanding of podocyte heterogeneity in ways bulk tissue analysis never could. The opportunity is enormous, but it also raises the bar for translational discipline. The challenge is no longer generating hypotheses. It is deciding which signals are biologically credible, clinically meaningful, and realistically actionable.

5. What are the biggest challenges in translating genetic and molecular insights into viable drug targets?

The jump from understanding the mechanism to having a druggable target remains genuinely hard. A few challenges stand out. First, many of the key pathways in rare kidney diseases involve structural proteins or transcription factors that are difficult to drug with conventional small molecules. Second, there is a validation problem. Our preclinical models, while improving, do not always recapitulate human disease faithfully enough to give us confidence before committing to clinical development. Third, and this is often underappreciated, rare diseases can have heterogeneous molecular subtypes within the same clinical diagnosis, so a target that is highly relevant for one patient subset may be irrelevant for another. That means stratifying patients early, which adds complexity and cost to already difficult programs. We also need to be honest that viability is not just a biological question. It is a development question—can we identify the right patients, define a feasible endpoint strategy, and generate evidence in a population small enough that every design choice matters? And viability is not only about development and regulatory feasibility. It also depends on payers recognising the broader value these therapies can create by helping patients stay healthier, reducing downstream complications, and lowering total healthcare utilisation over the course of a lifetime.

6. How is the field progressing in identifying reliable surrogate endpoints for rare kidney diseases with limited natural history data?

We have made real progress, but we are not where we need to be. eGFR remains the workhorse, but it is a lagging indicator, especially in paediatrics, where early intervention matters most. Proteinuria is useful, but limited as a standalone endpoint. What is encouraging is the serious investment in earlier and more sensitive biomarkers and the growing willingness of regulators to engage on qualification pathways. In small populations, surrogate endpoints are not an academic issue. They are often the difference between a study that is merely interesting and one that is feasible, ethical, and capable of supporting meaningful decisions. We also have concrete examples of progress: in IgA nephropathy, proteinuria has supported accelerated approvals; in FSGS, PARASOL has advanced the case for proteinuria as a more credible endpoint; in Alport syndrome, ASSENT is building the global dataset strategy needed for qualification; and similar endpoint-enabling work is underway in CAKUT through efforts such as the TRACK Consortium. But this progress is still disease-specific and uneven, and in many rare kidney diseases, we still lack the longitudinal data and validation packages needed to truly implement surrogate endpoints.

7. What role do novel biomarkers play in accelerating clinical decision-making and regulatory acceptance in renal drug development?

Biomarkers are where I think the field is approaching a real inflection point. We are moving from biomarkers as exploratory endpoints to biomarkers as decision tools for patient selection, risk stratification, treatment monitoring, accelerated approval, and regulatory qualification. In rare kidney disease, that matters enormously because it creates a more realistic path to development in small populations and can shorten the time to patient access. It also reinforces the need to study biomarkers in both adult and pediatric populations so we can support extrapolation where appropriate and move more quickly from adult proof of concept to meaningful access for children. For regulatory acceptance, the key is pairing analytical validity with clinical utility and building that case prospectively. The excitement is justified, but the evidence base is still thinner than what routine regulatory use will ultimately require.

8. What innovations in clinical trial design are helping overcome challenges in patient recruitment, retention, and stratification in rare renal diseases?

The biggest innovation has been the shift toward adaptive, pragmatic trial designs that can accommodate small, heterogeneous populations without sacrificing rigor. Basket designs, seamless Phase 2/3 studies, pediatric extrapolation, and Bayesian approaches are all helping reduce burden and make better use of limited data. Just as important is bringing trials closer to where patients are and where families feel comfortable, rather than expecting rare disease families to organise their lives around distant centers. That means relying more on local clinicians, community resources, and the patient community itself to help operationalise studies. Because these populations are so small, trial design has to be highly customised, grounded in a deep understanding of the disease, the available data, and the risk factors and stratification tools that best align with the endpoints being studied. The challenge is that operationalising these models consistently is still much harder than the rhetoric suggests.

9. How are digital tools, EHR systems, and centralised trial matching platforms improving efficiency in rare kidney disease studies?

The promise of digital tools has exceeded the reality so far, but we are closing the gap. EHR-based patient identification has improved feasibility and recruitment timelines in some programs, especially when registries are linked to clinical data systems. Platforms such as Natera and NEPTUNE Match can also help identify patients who are most likely to answer a scientific question and connect them to trials that may benefit them as individuals. The next frontier is using longitudinal EHR and registry data not just for recruitment, but for external control arms and more efficient development strategies. For that to be credible, however, these data have to meet the rigorous expectations of regulators, and often they do not. Making real-world data more complete, standardised, and fit for regulatory use is essential. Right now, these tools are often more helpful for feasibility and recruitment than for the more ambitious regulatory uses people often envision.

10. How can the industry better engage diverse patient populations and ensure more inclusive participation in rare kidney disease trials?

This is an area where the field still has a real accountability gap. Rare kidney diseases do not discriminate by race or socioeconomic status, yet our trial populations consistently underrepresent many of the communities most affected. Part of that is structural: sites are concentrated at large academic centers, and participation often requires time, travel, childcare, and financial flexibility that not all families have. Inclusive research requires intentional design from the beginning: where we place sites, how we communicate, what support we provide, and whether patients see themselves reflected in the research enterprise at all. It also requires sponsors to build real relationships with patient communities. If you want to solve problems in a rare disease, you have to become a true partner long before recruitment begins. And in a field that has gone from a therapeutic desert to a period of real opportunity, I worry the pendulum can swing too far toward speed over quality. In moving quickly, we risk sacrificing the harder foundational work of asking the right questions and building the trust and infrastructure with patient communities that make trials meaningful and durable.

11.  What strategies are proving most effective in improving the patient journey from diagnosis to therapy initiation?

The biggest lever is shortening the diagnostic odyssey. Families often spend years cycling through diagnoses before reaching the right one, and every year of delay can mean disease progression that cannot be recovered. Strategies that are working include embedding genetic counselors in nephrology practices, disease-specific care coordination, and advocacy-driven awareness efforts that prompt earlier referral. But diagnosis alone is not enough. Families also need a clearer path from diagnosis to education, care coordination, trial awareness, and treatment access. The strongest programs treat this as a care delivery problem, not just a medical one.

12.  How are emerging technologies such as kidney-on-a-chip models and advanced pre-clinical platforms changing translational research?

These platforms are genuinely exciting and could meaningfully improve translational research, although most are still earlier in validation than the enthusiasm sometimes suggests. Kidney-on-a-chip models capture aspects of renal physiology that static cell culture cannot, and patient-derived iPSC models allow us to study disease in the genetic background of actual patients without invasive tissue collection. Combined with CRISPR-based editing, these systems can accelerate target validation and help us de-risk decisions earlier. In rare disease, where every development step is costly in time and opportunity, better preclinical translation can have an outsized impact.

13.  What role do collaborations between pharma, biotech, academia, and patient advocacy groups play in accelerating therapeutic development?
 
Collaboration is not optional in rare kidney disease. The patient populations are too small and the scientific and operational challenges too complex for any single organisation to go it alone. The strongest collaborations combine complementary strengths across academia, industry, patient advocacy groups, and regulators. Patients and families are not just stakeholders in these efforts. They are essential strategic partners, and the best programs involve them early enough to shape the questions, not just react to the answers. What makes these collaborations work is alignment on goals, transparency about incentives, and shared clarity on the path to regulatory approval. Where they often break down is data sharing, which is why pre-competitive consortia and shared infrastructure matter so much. The language of collaboration is common now, but the willingness to share data and build truly cross-sector models is still far from routine.

14.  Looking ahead to the next 3–5 years, what breakthroughs or disruptive innovations do you expect will most transform rare and genetic kidney disease treatment?
 
A few things feel genuinely close. Gene therapy and gene editing are advancing rapidly in monogenic kidney diseases, and the question is increasingly not whether they can work, but whether we can deliver them safely and durably to the kidney, which remains a harder target organ than the liver or eye. We also need better ways to distinguish the most promising programs earlier so strong science can succeed and weaker candidates can be identified sooner, allowing us to use limited resources more wisely. I also expect progress in newborn genomic screening, which could enable pre-symptomatic intervention in early-onset genetic kidney diseases, especially in children. More broadly, the next wave of progress will come from combining scientific precision with development pragmatism: earlier diagnosis, better patient enrichment, more meaningful endpoints, and trial strategies built for small populations rather than borrowed from common diseases. Cross-sponsor and cross-industry partnerships will be essential, particularly around shared trial data. In rare kidney disease, keeping data siloed slows the science, weakens biomarker and endpoint validation, and ultimately delays therapeutic progress for patients. But none of this becomes transformative unless the field gets much better at execution, evidence sharing, and deciding earlier which programs are truly ready to advance.