Our Take
Nephrology sponsors have known for a decade that traditional endpoints move slowly; biomarkers exist to compress that timeline, but regulators treat novel markers as exploratory toys rather than decision levers.
Why it matters
Phase III renal trials cost $29.82 million and run nearly three years on average (per GlobalData), with enrollment alone taking 21.9 months. Sponsors funding these programs need decision signals now, not at trial close. Novel biomarkers like NGAL and KIM-1 detect injury mechanisms creatinine cannot, but uneven regulatory acceptance across regions and low specificity keep them from becoming primary endpoints.
Do this week
Sponsors: audit your Phase II protocol this quarter to confirm NGAL or KIM-1 collection is planned, so you can generate exploratory mechanistic data before Phase III enrollment locks in.
Nephrology trials are slow and expensive. Biomarkers offer earlier signals.
Phase III chronic kidney disease studies run an average of 34.7 months, with enrollment taking 21.9 months (per GlobalData analysis). Because kidney disease progresses slowly and many trials are event-driven (concluding only after a specific number of kidney failure or death endpoints are reached), sponsors face a capital-intensive waiting period before efficacy can be measured.
The financial stakes are severe. Phase II nephrology trials cost $20.57 million on average; Phase III jumps to $29.82 million (per GlobalData). Sponsors also contend with a crowded competitive landscape. The volume of new glomerulonephritis studies tripled in six years: 37 new studies in 2019 versus 111 in 2025. By the time a trial concludes, new therapies or updated treatment guidelines may have emerged, potentially invalidating results and requiring additional trials to align with current care standards.
Biomarkers are used in approximately 47% of all nephrology trials (per GlobalData), but usage skews heavily toward Phase II and Phase III studies (17% in Phase I). The majority deployed biomarkers measure efficacy, followed by patient screening and safety monitoring.
Traditional biomarkers like serum creatinine, eGFR, and proteinuria have known limitations. Creatinine is influenced by age, sex, diet, and muscle mass, producing false readings in certain subgroups. Proteinuria fluctuates based on hydration status and exercise. Novel biomarkers like neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin-C can detect injury mechanisms and early-stage dysfunction that traditional measures cannot capture.
NGAL and KIM-1 are particularly valuable in acute kidney injury trials because they are expressed in tubular cells after injury occurs, allowing researchers to distinguish true structural damage from temporary hemodynamic effects such as blood pressure fluctuations. Since 2022, 13% of new AKI clinical trials have used NGAL; KIM-1 has been used in just 5% (per GlobalData).
Regulatory acceptance lags behind clinical utility.
Novel biomarkers remain exploratory in the regulatory view. They are not yet accepted as primary endpoints, and adoption is uneven across regions, with stronger acceptance in the US than Europe. NGAL also suffers from low specificity: it is produced during inflammation or infection of various tissue types, not just kidneys, creating false positive concerns.
Dr. Henry Cremisi, Executive Medical Director of Medical Affairs at Caidya and a practicing nephrologist, noted that "biomarker use has lagged in nephrology. It is starting to tick up, but we are 20 years behind where oncology is." He emphasized that the key value of emerging injury biomarkers lies in their ability to distinguish true structural injury from temporary hemodynamic effects, allowing sponsors and researchers to avoid terminating promising drugs based solely on creatinine fluctuations.
Despite regulatory hesitation, these biomarkers already provide mechanistic insights vital for competitive differentiation. They can confirm whether a drug hits its intended molecular target before functional change is observed, inform optimal dosing, and reveal potential extrarenal indications that might justify basket trials in Phase III.
The missed opportunity is most acute in Phase I. Early biomarker use can detect safety signals and inform dose selection long before Phase III, reducing the cost and risk of failure at later stages.
Start collecting novel biomarker data now, even if regulators won't accept it yet.
Sponsors entering nephrology should treat NGAL and KIM-1 not as regulatory endpoints but as decision instruments and mechanistic proof points. Collecting this data early provides three concrete benefits: it shortens the decision timeline by revealing mechanism-of-action signals before traditional endpoints move, it builds a narrative of drug differentiation in a crowded field, and it generates evidence that may support regulatory acceptance as these markers mature and usage becomes more consistent across trials.
As the evidence base strengthens and novel markers are used more consistently, regulators are expected to move them from exploratory status to central trial components. Sponsors who begin collection now will have a head start in demonstrating utility once that transition occurs.