Long-Term Renal Benefit with Nefecon in Chinese Patients with Primary Immunoglobulin A Nephropathy: Two-Year NefIgArd Trial Results

Background: Immunoglobulin A (IgA) nephropathy (IgAN) is most prevalent in people of East Asian ancestry. Nefecon is a novel targeted-release oral budesonide product designed to act in the distal ileum to reduce excess galactose-deficient IgA1 production. The 2-year NefIgArd trial demonstrated that Nefecon 16 mg/day for 9 months led to a statistically significant treatment benefit on estimated glomerular filtration rate (eGFR) with Nefecon vs placebo. Here, we present results for all patients enrolled in NefIgArd from mainland China, including previously unreported patients. Methods: NefIgArd was a global, double-blind Phase 3 study. Patients with primary IgAN on optimized supportive care were randomized 1:1 to 9 months of Nefecon 16 mg/day or placebo, followed by a 15-month observational period off study drug. The 9-month primary endpoint was change in urine protein-creatinine ratio (UPCR). The 2-year primary endpoint was time-weighted average of eGFR over 2 years. Results: Baseline characteristics of all 62 Chinese patients were similar to the global study population and were balanced across treatment arms. There was a 9.58 mL/min/1.73 m2 (95% CI 1.95, 19.78) treatment benefit in the 2-year primary endpoint with Nefecon vs placebo (3.74 vs 13.32 mL/min/1.73 m2 average eGFR decline, respectively). At 24 months, the mean absolute changes in eGFR from baseline (Fig. 1) suggested that 66% of the eGFR decline observed with placebo could be prevented with 9 months of Nefecon treatment. Mean UPCR reduction was 31% greater at 9 months and 52% greater over 12-24 months with Nefecon vs placebo. No new safety signals were identified.Figure 1:: Mean change in eGFR at 9 and 24 monthsConclusions: Compared with placebo, 9 months of Nefecon treatment provided clinically relevant preservation of eGFR and durable proteinuria reduction over 2 years, supporting a disease-modifying effect in Chinese patients with primary IgAN. Funding: Commercial Support - Calliditas Therapeutics AB; Everest Medicines Ltd.