APPLAUSE-IgAN: Iptacopan improves proteinuria in IgA nephropathy

Interim results from the ongoing phase 3 APPLAUSE-IgAN trial showed that iptacopan significantly improved proteinuria with acceptable safety in participants with IgA nephropathy versus placebo.

Iptacopan is a complement factor B inhibitor which showed significant improvement in haemoglobin levels without transfusion in 2 recent phase 3 trials in participants with paroxysmal nocturnal haemoglobinuria [1]. The current APPLAUSE-IgAN (NCT04578834) investigates a 24-month treatment with iptacopan compared with placebo in a phase 3, multicentre, randomised, double-blind phase 3 setting in participants with primary IgA nephropathy. Eligibility criteria were biopsy-confirmed IgA nephropathy and a 24-hour urine protein-creatinine ratio ≥1 g/g despite maximally tolerated renin-angiotensin system inhibitors with/without sodium-glucose transport protein 2 (SGLT2) inhibition. The interim analysis's primary endpoint was a reduction in urine protein-creatinine ratio from baseline at month 9. The analysis included 250 participants for efficacy and 443 participants for safety (based on the study population at data cut-off) and Prof. Vlado Perkovic (University of New South Wales, Sydney, Australia) presented the results [2].

Iptacopan met the primary endpoint of the interim analysis at 9 months: 24h urine protein-creatinine ratio was reduced by 43.8% with iptacopan versus 9.0% with placebo, corresponding to a 38.3% difference between groups (95% CI 26.0–48.6; P<0.0001). These reductions in proteinuria were consistent among subgroups characterised by sex, geographic region (Asia vs non-Asia), various baseline urine protein-creatinine ratio categories, eGFR categories (30 to <45 vs <30 mL/min/1.73 m²), and participants with/without baseline use of SGLT2 inhibitors. In total, 8.1% of participants reported serious adverse events with iptacopan compared with 5.0% with placebo. Upper respiratory tract infections were more common with iptacopan (9.0% vs 7.2%), while adverse events such as nasopharyngitis (5.0% vs 7.2%), headache (4.1% vs 5.4%) and hypertension (1.8% vs 5.9%) were more common in the placebo arm. There were no deaths reported for either treatment regimen [2].

To conclude the interim analysis of APPLAUSE-IgAN showed the superiority of iptacopan over placebo in reducing proteinuria after 9 months of treatment in participants with IgA nephropathy. Overall, iptacopan was well-tolerated. The study is currently ongoing with a total treatment duration of up to 2 years [2].

1. de Latour RP, et al. N Engl J Med. 2024;390(11):994–1008.
2. Perkovic V, et al. Efficacy and safety of iptacopan in patients with primary IgA nephropathy: Interim analysis results of the Phase 3 APPLAUSE-IgAN study. Abstract #456, ERA 2024, 23–26 May, Stockholm, Sweden.

Medical writing support was provided by Mihai Surducan, PhD.

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Posted on 20 June 202424 June 2024