Efficacy and safety of a targeted-release formulation of budesonide in patients with primary IgA nephropathy (NefIgArd): 2-year results from a randomised phase 3 trial.
In the phase 3 NefIgArd trial, a 9-month course of targeted-release budesonide (Nefecon) produced a statistically significant slowing of eGFR decline and a durable reduction in proteinuria over 2 years versus placebo in patients with primary IgA nephropathy, supporting a disease-modifying effect.
Background
IgA nephropathy is a chronic immune-mediated kidney disease and a major cause of kidney failure worldwide, with the gut mucosal immune system implicated in its pathogenesis. Nefecon is a novel oral, targeted-release formulation of budesonide designed to act at the gut mucosal level, and the NefIgArd trial tested whether it could modify disease course on top of optimized supportive care.
Study design
This phase 3, multicentre, randomised, double-blind, placebo-controlled trial enrolled 364 adults with primary IgA nephropathy, eGFR 35-90 mL/min per 1.73 m2, and persistent proteinuria (UPCR at least 0.8 g/g or proteinuria at least 1 g/24 h) despite optimised renin-angiotensin system blockade, across 132 sites in 20 countries (NCT03643965). Patients were randomized 1:1 to 16 mg/day oral Nefecon or matching placebo for 9 months, followed by a 15-month off-drug observational period. The primary endpoint was the time-weighted average of eGFR over 2 years.
Key findings
The time-weighted average eGFR over 2 years favored Nefecon over placebo, with a difference of 5.05 mL/min per 1.73 m2 (95% CI 3.24 to 7.38; p<0.0001); the time-weighted average change was -2.47 mL/min per 1.73 m2 with Nefecon versus -7.52 mL/min per 1.73 m2 with placebo. The most common treatment-emergent adverse events with Nefecon were peripheral oedema (17 percent vs 4 percent), hypertension (12 percent vs 3 percent), muscle spasms (12 percent vs 4 percent), and acne (11 percent vs 1 percent). No treatment-related deaths occurred.
Clinical implications
A time-limited 9-month course of Nefecon delivered a clinically relevant reduction in eGFR decline and a durable reduction in proteinuria, supporting a disease-modifying effect in IgA nephropathy. The drug was well tolerated, with a safety profile as expected for a locally acting oral budesonide product. These results provide evidence for gut-directed budesonide as a targeted addition to optimized supportive care in this population.
Category
Research
Source
Lancet
More from ASNRT News
Browse the latest news, society announcements, KDIGO guideline updates, and AJNT issue releases on the ASNRT newsroom.