Irbesartan, Sparsentan Treatment Demonstrate Significantly Slower Kidney Function Decline Compared with SoC

Wu Gong, MD, MS

Credit: ResearchGate

A matching-adjusted indirect comparison (MAIC) revealed patients with immunoglobulin A nephropathy (IgAN) treated with either sparsentan or maximally tolerated irbesartan experienced significantly slower declines in kidney function compared with standard of care (SoC), according to a late-breaking presentation at the National Kidney Foundation (NKF) 2024 Spring Clinical Meeting. These results were observed in both real-world and clinical trial settings.¹

“Results from this study provide important context for the performance of treatments evaluated in the PROTECT trial,” wrote Wu Gong, MD, MS, and a team of investigators from Travere Therapeutics, Analysis Group, JAMCO Pharma Consulting, Ohio State University, and the University of Leicester.

As there is an absence of head-to-head trials in IgA nephropathy, the PROTECT trial examined the potential long-term nephroprotective benefits of sparsentan compared with the active control, irbesartan, among this patient population. After randomization, most (97%) patients receiving irbesartan were treated with the maximum labelled dose.

The phase 3, randomized, double-blind PROTECT trial included 202 patients receiving sparsentan and 202 patients receiving irbesartan. Investigators also sourced data from patients with IgAN within the UK National Registry of Rare Kidney Diseases (RaDaR) who received SoC (n = 535) and aggregated data from the control arm of the phase 3, randomized, double blind NefIgArd trial in patients with IgAN (n = 182). Patients in the control arm received placebo plus optimized and stable renin-angiotensin system (RAS) inhibitor therapy.

The primary outcome was the annualized 2-year decline in estimated glomerular filtration rate (eGFR) post-randomization in the PROTECT and NefIgArd trials or in the beginning of follow-up in the RaDaR trial. Matching-adjusted 2-year eGFR total slopes were estimated from the irbesartan and sparsentan cohorts and compared with the 2-year eGFR slopes in the RaDaR and NefIgArd trials.

Before matching, patients in the PROTECT trial were older in age, had a higher proportion of Asian patients, a lower proportion of White patients, exhibited lower systolic blood pressure (SBP), lower eGFR levels, and a longer duration since biopsy when compared with the RaDaR population. Compared with patients in the NefIgArd trial, patients in the PROTECT trial were also older in age, had higher blood pressure, reported a higher proportion of baseline diabetes, had a longer duration since biopsy, lower eGFR levels, and lower urine protein levels.

All matched effect modifiers and prognostic factors were balanced between cohorts after weighting, with a baseline mean age of 43.0 years, 68% were male, 75% were White, and the median eGFR levels were 55.00 ml/min/1.73².

Findings demonstrated a slower decline in kidney function in sparsentan-treated patients, and in those treated with maximally tolerated irbesartan, compared to real-world SoC from RaDaR and optimized—as defined by clinicians—SoC in NefIgArd.

In the PROTECT trial, a 2-year eGFR total slope difference of 1.12 ml/min/1.73² per year for those receiving irbesartan (P = .0239) and 1.89 ml/min/1.73² per year in the sparsentan cohort (P = .0004) was observed compared with the RaDaR trial.

Similarly, a difference of 1.30 ml/min/1.73² per year in the irbesartan cohort (P = .0395) and 2.26 ml/min/1.73² per year in the sparsentan cohort (P = .004) was reported in the PROTECT trial compared with the NefIgArd control cohort.

Investigators noted limitations including basing the analysis on source populations, which may hinder generalizability. Additionally, they could only assess known baseline factors that were consistently reported among the data sources and could not adjust for unmeasured or unreported variables.

“These results highlight the importance of considering the 2-year eGFR total slope difference between arms of the PROTECT trial in the context of what is achieved in current clinical practice,” investigators concluded.

References

1. ^{Gong W, Diva U, Bensink, M, Chai X, et al. Matching-Adjusted Indirect Comparisons of eGFR slopes in the PROTECT study with UK RaDaR IgA Nephropathy population and the control arm of NefIgArd. Poster presented at: National Kidney Foundation 2024 Spring Clinical Meeting (SCM). Long Beach, CA. May 14 – 18, 2024.}