The new delayed-release budesonide formulation Nefecon slows the rate of decline in the estimated glomerular filtration rate (eGFR) in patients with primary immunoglobulin A nephropathy (IgAN), reports a placebo-controlled trial in Kidney International.
Nefecon is a targeted formulation designed to deliver the oral glucocorticoid budesonide locally in the ileum, with limited systemic exposure. In the previous phase 2b NEFIGAN trial, Nefecon treatment was associated with greater reduction in the urine protein-to-creatinine ratio (UPCR) and a smaller decline in the eGFR in patients with IgAN at risk of kidney failure.
The phase 3 Efficacy and Safety of Nefecon in Patients with Primary IgA Nephropathy (NefIgArd) study was designed to verify those results. The first phase of the multicenter trial enrolled 199 patients with primary IgAN, persistent proteinuria, and an eGFR between 35 and 90 mL/min/1.73 m2. All had received optimized supportive care, including at least 3 months of stable renin-angiotensin system blockade.
Patients were randomly assigned to receive 9 months of treatment with Nefecon (16 mg/day) or placebo, followed by a 3-month observation period. The primary outcome was 24-hour UPCR at the end of treatment. Secondary outcomes included eGFR at 9 and 12 months and UPCR at 12 months.
At 9 months, UPCR had decreased by 31% from baseline in patients receiving Nefecon compared with 5% in the placebo group. Results were consistent in subgroup analyses. Patients in the Nefecon group had continued improvement after treatment's end, including a 48% reduction in UPCR at 12 months. Nefecon was also associated with a slower decline in eGFR: a 3.87 mL/min/1.73 m2 difference compared with placebo. T reatment was well tolerated, with mild to moderate, reversible adverse events.
The first phase of NefIgArd “supports Nefecon as the first disease-modifying therapy approved for patients with primary IgAN at risk of kidney failure,” the researchers write. An observational follow-up phase is underway to verify the long-term impact on kidney function [Barratt J, et al. Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy. Kidney Int, published online ahead of print October 19, 2022. doi: 10.1016/j.kint.2022.09.017;https://www.kidney-nternational.org/article/S0085-2538(22)00836-5/fulltext].
