Long-term efficacy and safety for the complement factor B inhibitor iptacopan in IgA nephropathy
In brief
Iptacopan slowed annual kidney decline from 5.29 to 2.11 in IgA nephropathy
In an open-label extension, patients who switched from placebo to iptacopan saw annual kidney function loss slow from 5.29 to 2.11 milliliters per minute per 1.73 square meters over the next two years. Proteinuria reductions persisted for up to four years, with no new safety signals over as long as five years, but the extension lacked a placebo comparison.
- Journal
- Kidney international (Q1)
- Published
- 22 October 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Brad H Rovin, Hernán Trimarchi, Bart Maes, Vlado Perkovic, Naoki Kashihara, Hong Zhang, et al.
- PMID
- 42909451
- DOI
- 10.1016/j.kint.2026.09.017
Why clinicians should know about it
- Picked for Nephrology (paper of the day, 25 October 2026): Long-term phase III extension reports IgA nephropathy treatment outcomes
Abstract
INTRODUCTION: Iptacopan, a factor B inhibitor, targets alternative complement pathway overactivation, a key driver of glomerular inflammation in IgA nephropathy. In the phase 3 APPLAUSE-IgAN trial (NCT04578834), iptacopan significantly slowed kidney function decline versus placebo over 24 months (difference in total estimated glomerular filtration rate [eGFR] slope: 3.02 ml/min per 1.73 m2 per year [95% confidence interval (CI) 2.02, 4.01; P < 0.001]). METHODS: Patients who completed APPLAUSE-IgAN or the phase 2 iptacopan trial (NCT03373461) could enter an open-label rollover extension program (REP) (NCT04557462). Patients in this REP receive oral iptacopan 200 mg twice daily alongside supportive care. Patients from the phase 2 trial were not included in efficacy analyses. RESULTS: Overall, 194 and 174 patients from the APPLAUSE-IgAN iptacopan and placebo arms, respectively, entered the REP. In patients who received iptacopan for up to 48 months, the total annualized eGFR slope was -3.49 ml/min per 1.73 m2 per year (95% CI -4.17, -2.80). Urine protein-to-creatinine ratio from first morning void (UPCR-FMV) reduction was sustained through 48 months with iptacopan (geometric mean ratio to baseline: 0.61 [95% CI 0.50, 0.75]). Before receiving iptacopan, the total eGFR slope over 24 months in APPLAUSE-IgAN placebo arm patients who entered the REP was -5.29 ml/min per 1.73 m2 per year (95% CI -6.09, -4.49). After switching to iptacopan, the total eGFR slope improved to -2.11 ml/min per 1.73 m2 per year (95% CI -3.08, -1.13) over the next 24 months. UPCR-FMV decreased after switching (geometric mean ratio to baseline at month 48: 0.74 [95% CI 0.59, 0.91]). Long-term safety up to 5 years (median treatment duration: 29.9 months) was consistent with the known profile of iptacopan. CONCLUSIONS: Long-term treatment with iptacopan led to sustained slowing in eGFR decline and proteinuria reduction that were also observed after switching from placebo. No new safety signals were observed. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study numbers NCT04578834 (APPLAUSE-IgAN), NCT03373461 (phase 2 trial of iptacopan in IgAN), and NCT04557462 (rollover extension program).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.