#3251 Nefecon provides kidney benefit irrespective of time since diagnosis in patients with IgAN: a subanalysis of the NefIgArd study

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is a chronic immune-mediated kidney disease characterized by galactose-deficient IgA1 (Gd-IgA1) deposition in the glomeruli. The Peyer's patches of the gut-associated lymphoid tissue are a major site of Gd‑IgA1-producing B cells. Nefecon is an oral targeted-release formulation of budesonide, which targets drug release into the distal ileum. Nefecon has been shown to reduce the loss of kidney function in adults with primary IgAN who are at risk of disease progression. Results from the Phase 3 NefIgArd study demonstrated that nefecon 16 mg/day reduced proteinuria and preserved estimated glomerular filtration rate (eGFR) over 9 months of treatment. Proteinuria and eGFR benefit were sustained for up to 15 months of observational follow-up in patients with primary IgAN. Since IgAN is a progressive disease, early diagnosis and intervention in IgAN are pivotal to slow the irreversible loss of nephrons and prevent progression to kidney failure. Here, we present results from a subanalysis of the NefIgArd study evaluating the effect of nefecon 16 mg/day according to time since IgAN diagnosis by biopsy at baseline. Method NefIgArd study design and study endpoints have been previously described. Briefly, eligible patients were aged ≥18 years with biopsy-confirmed primary IgAN diagnosed within the past 10 years, eGFR 35–90 mL/min/1.73 m2, persistent proteinuria ≥1 g/24 hours despite optimized renin–angiotensin system (RAS) inhibition, and well-controlled blood pressure. Patients received nefecon 16 mg/day or placebo for 9 months (n = 182 per treatment group) in addition to supportive care (RAS inhibition), followed by a 15-month observational period on supportive care only. This subanalysis reports eGFR and urine protein–creatinine ratio (UPCR) change over time during the NefIgArd study. Patients were divided into quartiles according to time since IgAN diagnosis by biopsy at baseline. Results Mean time since diagnosis was 4.3 years in the overall population (Table 1). Quartile 1 was <0.6 years since diagnosis, quartile 2 was 0.6 to <2.4 years since diagnosis, quartile 3 was 2.4 to <6.4 years since diagnosis, and quartile 4 was ≥6.4 years since diagnosis. Nefecon, compared with placebo, was associated with eGFR benefit across all quartiles. In patients diagnosed <0.6 years prior to baseline, eGFR was preserved with nefecon relative to placebo by +6.41, +5.78, and +4.79 mL/min/1.73 m2 at 9, 12, and 24 months, respectively. In patients diagnosed >6.4 years prior to baseline, eGFR was preserved with nefecon relative to placebo by +6.95, +3.61, and +5.07 mL/min/1.73 m2 at 9, 12, and 24 months, respectively. Nefecon was also associated with reduction in UPCR across all quartiles. In patients diagnosed <0.6 years prior to baseline, nefecon reduced UPCR versus placebo by 22.01%, 51.12%, and 18.52% at 9, 12, and 24 months, respectively. In patients diagnosed >6.4 years prior to baseline, nefecon reduced UPCR versus placebo by 16.74%, 42.88%, and 35.48% at 9, 12, and 24 months, respectively. Overall, patients diagnosed with IgAN <0.6 years prior to baseline maintained kidney function to a greater extent over the 2 years than other quartiles (Fig. 1). Conclusion This NefIgArd subanalysis demonstrated that nefecon conferred treatment benefit in all patients versus placebo, irrespective of time since diagnosis; however, nefecon preserved kidney function to a greater extent versus placebo in patients recently diagnosed with IgAN. This supports the benefit of early initiation of nefecon treatment to slow disease progression and loss of kidney function.

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