Filling the Gap by Targeting the Gut: First Disease-Modifying Treatment Approved for IgA Nephropathy

Abstract

This symposium took place during the 60th European Renal Association (ERA) Congress, held in Milan, Italy, and virtually. Bengt Fellström, Uppsala University, Sweden, described the relationship between IgA nephropathy (IgAN) and gastrointestinal mucosal reactivity. Fellström then outlined the history of Nefecon (Calliditas Therapeutics, Stockholm, Sweden, and STADA Arzneimittel, Bad Vilbel, Germany), which was developed based on the assumption that the gut plays a major role in the pathophysiology of the disease, and that there was a high unmet need for a well-tolerated and effective therapy. Nefecon was specifically designed to target the origins of IgAN. A Phase IIb clinical trial showed, for the first time, that 9 months of treatment with Nefecon was well-tolerated and effective in patients at risk of disease progression. Jonathan Barratt, University of Leicester, UK, and John Walls Renal Unit, Leicester General Hospital, UK, presented biomarker data supporting the efficacy data in clinical trials, and presented topline data from Part B of the Phase III NefIgArd trial. Specifically, the results demonstrated an average 5.05 mL/min/1.73 m2 estimated glomerular filtration rate (eGFR) treatment benefit in favour of Nefecon versus placebo over 2 years. This confirmed that the eGFR benefit of 9 months of active treatment with Nefecon was maintained during the observational follow-up. The eGFR benefit with Nefecon versus placebo was consistent regardless of baseline urine protein-creatinine ratio (UPCR). At 2 years, the 30% reduction in UPCR in the Nefecon versus placebo arm was similar to the percentage reduction at the end of the 9-month treatment period, plus 15 months follow-up off treatment. Patients treated with Nefecon experienced decreasing levels of proteinuria while on active treatment and for 3 months afterwards, suggesting a continued biologic effect. Barratt presented UK registry data showing that, despite being treated with the current standard of care for IgAN, three-quarters of adults and half of paediatric patients developed kidney failure or died within 20 years of disease onset. Barratt suggested a paradigm shift in the treatment approach for all patients with IgAN, who have a risk of developing kidney failure in their lifetime.