A novel targeted-release formulation of the corticosteroid budesonide (TRF-budesonide) could become the first tailored treatment for immunoglobulin A nephropathy (IgAN).
The oral medication delivers to the distal ileum, targeting mucosal immunity before disease appears. Due to its lower absorption, the drug may result in fewer and less severe side effects than high-dose systemic corticosteroids.
Bengt Fellström, MD, of Uppsala University Hospital in Uppsala, Sweden, led the NEFIGAN Trial to compare optimized renin-angiotensin system (RAS) blockade plus targeted-release budesonide with optimized RAS blockade alone. Of 150 IgAN patients, 48 were randomly assigned to 16 mg and 51 patients to 8 mg daily TRF-budesonide as an adjunct to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers titrated up to maximally recommended doses. Included patients had an estimated glomerular filtration rate (eGFR) of at least 45 mL/min/1.73 m2 and a urine protein creatinine ratio (UPCR) above 0.5 g/g or urinary total protein of at least 0.75 g/day, indicating persistent proteinuria.
After 9 months of treatment, mean UPCR fell by 27.3% in the 16 mg group and 21.5% in the 8 mg group, according to results published in the Lancet. Meanwhile, placebo patients experienced a 2.7% uptick in UPCR. Changes in 24-hour protein excretion, urine albumin to creatinine ratio, and 24-hour albumin excretion were in line with UPCR results. During the study period, eGFR remained stable with TRF-budesonide but fell 10% with placebo.
Such a reduction in proteinuria coupled with stabilization of eGFR in IgAN patients may reduce progression to end-stage renal disease. “The observed beneficial effect was additive to optimized RAS blockade and supports the use of TRF-budesonide as adjunct therapy in patients with IgA nephropathy with persistent proteinuria,” Dr Fellström concluded in a news release.
“In my opinion, this is the most important treatment trial conducted to date for IgA nephropathy,” Robert J Wyatt, MD, of the University of Le Bonheur Children’s Hospital in Memphis, Tennessee, commented in an accompanying editorial. “The results will potentially change treatment strategy for an important subset of patients with IgA nephropathy.”
Adverse events occurred in similar proportions of treated and untreated patients. The investigators suggested that 2 of 13 serious adverse events were possibly related to the drug: deep vein thrombosis in a patient receiving 16 mg and unexpected renal function decline in a patient tapered from 16 mg to 8 mg over 2 weeks.
The study was funded by Pharmalink AB, the makers of TRF budesonide (Nefecon).
1. FellstrÖm BC, Barratt J, Cook H, et al. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Lancet 2017;389:2117–27. doi:10.1016/S0140-6736(17)30550-0
2. Wyatt RJ. Are we ready for targeted therapy for IgA nephropathy? Lancet 2017. doi:10.1016/S0140-6736(17)30820-6
3. Novel targeted-release formulation of budesonide reduced proteinuria in IGAN patients. ERA-EDTA Congress; June 4, 2017. [news release]