Efficacy and Safety of Nefecon in Patients with IgA Nephropathy from Mainland China: 2-Year NefIgArd Trial Results

Abstract

Background: IgA nephropathy (IgAN), an immune-mediated kidney disease, is particularly prevalent among individuals of East Asian ancestry. Nefecon is a novel, oral, targeted-release budesonide formulation designed to inhibit galactose-deficient IgA1 formation underlying IgAN pathophysiology. We present findings in patients with IgAN from mainland China participating in the 2-year, multicenter, randomized, double-blind, phase 3 NefIgArd trial of nefecon.

Methods: Patients (aged 18 years and older) with primary IgAN (eGFR 35–90 ml/min per 1.73 m2, persistent proteinuria [urine protein–creatinine ratio ≥0.8 g/g or proteinuria ≥1 g/24 hours] despite optimized renin-angiotensin system blockade) received nefecon or placebo over 9 months, followed by a 15-month follow-up phase on supportive care alone. The primary efficacy end point was time-weighted average of eGFR over 2 years.

Results: Sixty-two patients from mainland China were included in this prespecified analysis. The primary efficacy end point was 9.6 ml/min per 1.73 m2 (95% confidence interval, 2.0 to 19.8) in favor of nefecon versus placebo. This was consistent with (and numerically greater than) that of the global study population. Time to confirmed 30% eGFR reduction or kidney failure from baseline was substantially delayed with nefecon (patients with an event: 9%) versus placebo (30%; hazard ratio, 0.21; 95% confidence interval, 0.04 to 0.73). No deaths were reported in the China cohort. In the nefecon group, treatment-emergent serious adverse events were reported by one patient during treatment and two patients during follow-up (versus no patients and seven patients, respectively, in the placebo group). No severe infections requiring hospitalization were reported.

Conclusions: Nefecon treatment for 9 months showed greater preservation of eGFR over 2 years compared with placebo. The efficacy outcomes were consistent with global study results, with a numerically greater treatment benefit observed in patients from China. Nefecon was well tolerated, with no unexpected safety signals.

Trial registration: ClinicalTrials.gov NCT03643965.

Graphical abstract

Figure 1

Mean (±SEM) absolute change in eGFR from baseline in the NefIgArd trial. (A) China cohort and (B) global study population (full analysis set). CI, confidence interval; NefIgArd, efficacy and safety of nefecon in patients with primary IgA nephropathy; SEM, standard error of the mean.

Figure 2

Time to confirmed 30% eGFR reduction or kidney failure—NefIgArd China cohort and global study population. Kidney failure was defined as dialysis for ≥1 month, kidney transplantation, sustained (≥1 month) eGFR <15 ml/min per 1.73 m², or kidney-related death. HR, hazard ratio; IPCW, inverse probability of censoring weighting. ^aThe HR was estimated using an IPCW method. The aim of the analysis was to estimate the HR in the absence of rescue using IPCW because censoring because of rescue was considered informative. The 95% CIs were calculated using a profile-likelihood method. ^bStandard Cox model, with 95% CIs calculated using a profile-likelihood method. HR, hazard ratio; IPCW, inverse probability of censoring weighting.

Figure 3

Mean (±SEM) percentage change in UPCR from baseline in the NefIgArd trial. (A) China cohort and (B) global study population (full analysis set). UPCR, urine protein–creatinine ratio.

Figure 4

Proportion of patients without microhematuria at baseline and during the observational period (12–24 months) in the NefIgArd China cohort and global study population. ^an represents the number of patients with two or more valid urine dipstick results during the observational period.