Daniel Gale, PhD, MB BChir, is the director of the UK-based RaDaR Registry and the St Peter's Chair of Nephrology at University College London.

 Daniel Gale, PhD, MB BChir

A new analysis from the phase 3 VALIANT trial reinforces the potential of pegcetacoplan (Empaveli) as a disease-modifying therapy for 

 and idiopathic immune-complex membranoproliferative glomerulonephritis (IC-MPGN).

Results of the study, which were presented at the 

62nd European Renal Association (ERA 2025) Congress

, suggest use of pegcetacoplan was associated with improvements in complement biomarkers, sustained reductions in proteinuria, and early signs of kidney protection.

“It’s an exciting trial to see those data and the 3 things that they showed was the striking 60% reduction in proteinuria, the really clear evidence of stabilization of GFR compared with a placebo arm that lost 7.5 mLs per minute in just 6 months, and, perhaps most strikingly, was the biopsy appearances, where 70% of the patients there was no C3 deposited on the biopsy after 6 months when it was present,” explained Daniel Gale, MBChB, PhD, director of the UK-based RaDaR Registry and the St Peter's Chair of Nephrology at University College London, in an interview.

In the 124-patient trial, participants received subcutaneous pegcetacoplan or placebo twice weekly for 26 weeks in addition to background therapy. The original results were presented at the American Society of Nephrology’s Kidney Week 2024 and demonstrated pegcetacoplan was associated with a statistically significant and clinically meaningful 68% (

 <.0001) reduction in proteinuria compared to placebo at week 26.

In the ERA 2025 study presented by Gale, the pegcetacoplan group showed robust complement rebalancing by week 4, with serum C3 rising by 308.7 mg/dL (SD, 94.7) and soluble C5b-9 decreasing by 612.3 ng/mL (SD, 614.7). Of note, no biomarker improvements were observed in the placebo group.

At week 26, 71% of pegcetacoplan-treated patients had complete clearance of glomerular C3c on biopsy. In terms of proteinuria, pegcetacoplan showed rapid and sustained effect: by week 4, reductions were apparent, and by week 26, 50.8% of patients (32/63) had UPCR less than 1 g/g, including 31.7% below 0.5 g/g. In contrast, the placebo arm showed no meaningful shift across proteinuria strata, with patients remaining in higher UPCR ranges or worsening.

In the study presented by Gale, investigators noted previous registry data show patients who achieve UPCR less than 0.88 g/g within the first year of diagnosis have an 87% reduction in long-term risk of kidney failure. In VALIANT, half of pegcetacoplan-treated patients reached this threshold by week 26.

To learn more about how pegcetacoplan could shift the treatment paradigm in C3G and IC-MPGN, watch our full interview with Dr Gale from ERA 2025.

Pegcetacoplan Could Halt Disease Progression in C3 Glomerulopathy, IC-MPGN, with Daniel Gale, PhD, MB BChir

 include Novartis, Alexion, Calliditas, Britannia, Vifor, Judo Bio, Adnovate, Sanofi, Anlylam, Boehringer Ingelheim, and Bayer.

Gale DP, Bomback AS, Licht C, et al. Pegcetacoplan Treatment Appears to Halt Disease Progression in C3G and Primary (Idiopathic) IC-MPGN Patients: Results from the Phase 3 VALIANT Study. Presented at: 62nd European Renal Association Congress. June 04 – 07, 2025. Vienna, Austria.

Campbell P. VALIANT: Pegcetacoplan Offers Benefit for UPCR, eGFR, C3 Staining in C3G, IC-MPGN. HCP Live. Published October 26, 2024. Accessed June 8, 2025. 

https://www.hcplive.com/view/valiant-pegcetacoplan-offers-benefit-for-upcr-egfr-c3-staining-in-c3g-ic-mpgn

Videos

An analysis of the VALIANT trial provides insight into the benefits of pegcetacoplan in patients with C3G and IC-MPGN. 

New data from the UK National Registry of Rare Kidney Diseases (RaDaR) provide the most detailed longitudinal analysis to date of kidney function decline in 

, reinforcing the critical role of genotype and proteinuria control in predicting long-term outcomes.

 by Daniel Gale, MBChB, PhD, director of the RaDaR Registry, the study included 1175 individuals with genetically or biopsy-confirmed AS and used national linkage data with multi-level modeling to track eGFR slope and proteinuria progression across 

 stages, with results stratified by genotype.

“In RaDaR, we’ve now got about 1100 people with Alport Syndrome, of whom over 500 we've got genetic information on. And we wanted to ask some of the same questions that we'd previously asked in [focal segmental glomerulosclerosis], obviously a smaller number of patients,” said Gale, in an interview with HCPLive.

Among 535 patients with genetic data, those with classical AS genotypes, including male X-linked, autosomal recessive, or digenic, exhibited significantly faster eGFR decline compared to heterozygous genotypes. The difference was most pronounced in CKD stage 4, with classical genotypes losing kidney function at –9.1 mL/min/1.73 m² per year (95% CI, –10.9 to –7.3) versus –3.8 mL/min/1.73 m² per year (95% CI, –5.5 to –2.1) for heterozygotes.

Proteinuria increased with CKD progression across the cohort, but a significant upward trajectory was observed only in male X-linked and autosomal recessive cases. Critically, patients with higher proteinuria levels before reaching eGFR thresholds of 90, 60, or 45 mL/min/1.73 m² had substantially worse kidney survival. Hazard ratios for kidney failure in patients above the median proteinuria were 5.3, 3.6, and 6.5, respectively, at those eGFR cutoffs.

In an interview at ERA 2025, Gale emphasized the importance of these findings not only for understanding disease progression in AS but also for clinical trial design. To learn more about how RaDaR is shaping research and accelerating trial readiness in rare kidney diseases like AS, watch our full interview with Dr Gale from ERA 2025.

Alport Syndrome Outcomes Linked to Genotype and Proteinuria in RaDaR Study

Daniel Gale, PhD, MB BChir, Alport Syndrome Outcomes Linked to Genotype and Proteinuria in RaDaR Study

Wong K, Pitcher D, Rogers D, et al. Kidney outcomes and effects of proteinuria in Alport Syndrome: a longitudinal analysis of 1175 patients from the UK National Registry of Rare Kidney Diseases (RaDaR). Presented at: 62nd European Renal Association Congress. June 04 – 07, 2025. Vienna, Austria.

A RaDaR analysis from ERA 2025 provides insight into predictors of disease progression, outcomes in patients with Alport syndrome. 

New results from the PARASOL consortium highlight the successful validation of proteinuria reduction as a surrogate endpoint for kidney failure in 

focal segmental glomerulosclerosis (FSGS)

, reinforcing its utility for future clinical trials. The validation, which leveraged the UK National Registry of Rare Kidney Diseases (RaDaR) registry, marks a critical step in establishing reliable, feasible endpoints for drug development in this rare and progressive condition.

The PARASOL initiative combined data from 9 registries across North America and Europe to identify markers that predict long-term outcomes in patients with biopsy-proven or genetic FSGS. Among 1626 eligible participants in the PARASOL cohort, reduction in UPCR to below 0.7 g/g by 24 months was associated with an 85% lower hazard of kidney failure (HR, 0.15; 95% CI, 0.09–0.26), along with a survival advantage of +0.27.

, these findings were independently validated in 465 patients from RaDaR, a longstanding national registry with phenotyping of patients with rare kidney diseases. Despite demographic and clinical differences, including older age, lower baseline eGFR, and higher baseline proteinuria, RaDaR participants showed similar predictive value for proteinuria response. At the 0.7 g/g threshold, responders had a hazard ratio for kidney failure of 0.07 (95% CI, 0.02 to 0.27) and a +0.29 survival difference, closely mirroring the PARASOL results.

Want to learn more about PARASOL? Check out this episode of Kidney Compass: Navigating Clinical Trials!

According to Daniel Gale, MBChB, PhD, director of the UK-based RaDaR Registry and the St Peter's Chair of Nephrology at University College London, validation in RaDaR represents a key milestone, demonstrating that findings from PARASOL are not confined to research settings or selective cohorts and confirming proteinuria response is a robust, reproducible surrogate endpoint that holds across diverse FSGS populations, including those captured in real-world clinical registries.

In an interview at ERA 2025, Gale noted this level of cross-cohort consistency supports the adoption of UPCR-based endpoints in clinical trials, offering a practical alternative to highly variable eGFR-based outcomes that would require much larger sample sizes to detect meaningful effects.

For more on this study, check out our interview with Gale from the floor at ERA 2025:

RaDaR Validation Confirms PARASOL Findings on FSGS Surrogate Endpoint, with Daniel Gale, PhD, MB BChir

Smith A, Pitcher D, Helmuth M, et al. Proteinuria as a clinical trial endpoint in focal segmental glomerulosclerosis: Validation of PARASOL findings in RaDaR. Presented at: 62nd European Renal Association Congress. June 04 – 07, 2025. Vienna, Austria.

A study presented at ERA 2025 validates the use of proteinuria as a surrogate endpoint for FSGS clinical trials. 

Daniel Gale, PhD, MB BChir

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