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Nefecon is a novel, oral, targeted-release capsule formulation of budesonide, designed to treat immunoglobulin A nephropathy (IgAN) by inhibiting IgA formation in the Peyer’s patch–rich distal ileum. Based on Phase 3 interim results, the US Food and Drug Administration and European Medicines Agency approved the use of Nefecon in patients with primary IgAN. Data collected over a 9-month period from the initial 199 patients with IgAN in the Phase 3 Efficacy and Safety of Nefecon in Patients With Primary IgA Nephropathy (NefIgArd) trial showed a significant reduction in urine protein–creatinine ratio (UPCR) and preservation of the estimated glomerular filtration rate (eGFR) with Nefecon versus placebo (Barratt J, et al. Kidney Int 2023;103(2):391-402). Here, we present data for the complete study population from the full 2-year trial, including 9 months of treatment and 15 months of follow-up off drug, with the aim to compare eGFR decline (measured as a composite endpoint of confirmed 30% reduction in eGFR from baseline or kidney failure) among patients who received either Nefecon 16 mg/day or placebo.
Eligible patients were aged ≥18 years, diagnosed with primary IgAN, had eGFR of 35-90 mL/min/1.73 m2, UPCR ≥0.8 g/g or proteinuria ≥1 g/24 h despite renin–angiotensin system blockade, and blood pressure <140/90 mmHg. To confirm a 30% reduction in eGFR from baseline, two values ≥4 weeks apart were required (calculated using the Chronic Kidney Disease Epidemiology Collaboration formula). Kidney failure was defined as dialysis for ≥1 month, kidney transplantation, sustained (≥1 month) eGFR <15 mL/min/1.73 m², or kidney-related death. Any data impacted by rescue medication were excluded from the primary analysis.
The full analysis set included 364 patients. Treatment with Nefecon for 9 months resulted in approximately 50% less deterioration of kidney function versus placebo at 24 months. Additionally, during the 9-month treatment period, Nefecon demonstrated a 30% reduction in UPCR compared with placebo, which was sustained for up to 2 years. The percentage of patients with a confirmed 30% reduction in eGFR or kidney failure was lower in the Nefecon arm than in the placebo arm (Figure 1). The time to a confirmed 30% reduction in eGFR or kidney failure event was significantly delayed with Nefecon versus placebo (hazard ratio [HR] 0.45; 95% confidence interval 0.26, 0.75]; p=0.0014 [1-sided]). A predefined supplementary analysis including rescue medication use as an event yielded similar results (HR 0.51). Notably, the treatment effect with Nefecon on the risk of 30% reduction in eGFR or kidney failure was consistent irrespective of baseline UPCR (UPCR <1.5 and ≥1.5 g/g, HR 0.51 and 0.42, respectively) (Figure 2). During the 9-month treatment period, Nefecon 16 mg/day was well tolerated, with a safety profile as expected for a locally acting oral budesonide product.
Conclusions
These findings strongly indicate preserved kidney function with Nefecon and provide support for Nefecon as a disease-modifying therapy in patients with IgAN.
This abstract was also submitted for the ASN’23 congress. By submitting the abstract to WCN’24, abstract authors declare that re-submitting the abstract is permitted by the organizers of the previous meeting.