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

Key Points In the NefIgArd trial China cohort, 9 months of nefecon treatment led to clinically relevant preservation of kidney function over 2 years. Durable proteinuria reduction was also observed over 2 years with 9 months of nefecon treatment. These results were consistent with those of the global study population and support the disease-modifying effects of nefecon. 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 m 2 , 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 m 2 (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. Clinical Trial registry name and registration number: Efficacy and Safety of Nefecon in Patients With Primary IgAN, NCT03643965.