Nefecon therapy arrests estimated glomerular filtration rate decline and proteinuria in IgA Nephropathy

A new study published in The Lancet suggested that 9-month Nefecon treatment resulted in a clinically significant decrease in eGFR decline and a long-lasting decrease in proteinuria compared to placebo, supporting a disease-modifying impact in individuals with IgA nephropathy.

IgA nephropathy is a chronic, immune-mediated kidney condition that is a major global contributor to kidney failure. Its pathophysiology has been linked to the gut mucosal immune system, and Nefecon, an oral formulation of budesonide with tailored release that is developed to work at the gut mucosal level.

Adult patients (aged 18 years) with primary IgA nephropathy, eGFR 35-90 mL/min per 173 m2, and persistent proteinuria (urine protein-creatinine ratio 08 g/g or proteinuria 1 g/24 h) despite improved renin-angiotensin system blockade were included at 132 hospital-based clinical sites in 20 countries worldwide. For 9 months, patients were randomly allocated (1:1) to receive 16 mg/day oral capsules of Nefecon or a matched placebo, followed by a 15-month longitudinal follow-up period off study medication. Randomization was stratified by baseline proteinuria (2 or 2 g/24 h), baseline eGFR, and geography (Asia-Pacific, North America, Europe, or South America) using an interactive response technology system.

Throughout the 2-year experiment, patients, investigators, and site personnel were kept in the dark about the therapy. Throughout the experiment, optimal supportive care was also provided. The primary effectiveness outcome was a 2-year time-weighted average of eGFR. The entire analytic set was subjected to efficacy and safety evaluations.

The key findings of this study were:

Between September 5, 2018, and January 20, 2021, participants were enrolled for the NefIgArd experiment, with 364 patients (182 per therapy group) randomly allocated in the whole analysis set.

240 (66%) of the patients were men, 124 (34% were women), and 275 (76%) were White.

Over a 2-year period, the time-weighted average of eGFR indicated a statistically significant treatment advantage with Nefecon over placebo, with a time-weighted average change of -247 mL/min per 173 m2 recorded with Nefecon and -752 mL/min per 173 m2 reported with placebo.

Peripheral edema, muscular spasms, hypertension, acne, and headache were the most often reported treatment-emergent side effects during Nefecon therapy.

Reference:

Lafayette, R., Kristensen, J., Stone, A., Floege, J., Tesař, V., Trimarchi, H., Zhang, H., Reich, H. N., Rovin, B. H., & Barratt, J. (2023). 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 Lancet. Elsevier BV. https://doi.org/10.1016/s0140-6736(23)01554-4