APPLAUSE-IgAN Interim Analysis Finds Iptacopan Safe, Effective

Although evidence suggests that the alternative complement pathway is involved in the pathogenesis of immunoglobulin A nephropathy (IgAN), there are currently no approved therapies that target it. The phase III APPLAUSE-IgAN study (NCT04578834) examined the use of iptacopan plus optimized supportive care in IgAN. Dmitrij Kollins and colleagues reported results of nine-month prespecified analyses of APPLAUSE-IgAN data.

The randomized, double-blind, placebo-controlled study included patients with biopsy-confirmed IgAN and proteinuria ≥1 g/g by urine protein-to-creatinine ratio from 24-hour urine collection (UPCR-24h) despite receiving maximally tolerated renin-angiotensin-aldosterone inhibitors for three months or longer. Patients were randomized 1:1 to receive iptacopan, 200 mg, twice daily or placebo.

The interim efficacy analyses included 125 participants in each study group. The interim safety analyses included 222 patients in the iptacopan group and 221 in the placebo group. Baseline characteristics were balanced between the two treatment groups.

Iptacopan reduced UPCR-24h by 38.3% from baseline to month nine relative to placebo (95% CI, 26%-48.6%; one-sided P<.0001). It also decreased UPCR from first morning void as early as week two, and the effect continued through month nine, with a reduction of 35.8% (95% CI, 22.6%-46.7%) relative to placebo at month nine. Nearly twice as many patients in the iptacopan group (marginal proportion, 42.5%; 95% CI, 34.5%-50%) achieved UPCR-24h less than 1 g/g at month nine than those in the placebo group (21.9%; 95% CI, 14.8%-29.0%).

In addition, iptacopan was well tolerated. Treatment was discontinued due to adverse events among 2.7% of participants in each group, and the infection rate in the iptacopan group did not exceed that of the placebo group.

In conclusion, the interim APPLAUSE-IgAN data showed that iptacopan was superior to placebo at reducing proteinuria at nine months. The positive effect was seen early and remained consistent. In addition, the drug was well tolerated and demonstrated a favorable safety profile.

Source: Kollins D, Papachristofi O, Hach T, et al. Efficacy and safety of iptacopan in patients with IgA nephropathy (IgAN): interim analysis (IA) of the phase 3 APPLAUSE-IgAN study. #WCN25-799. Presented at the World Congress of Nephrology; February 6-9, 2025; New Delhi, India. This abstract was also presented at the National Kidney Foundation Spring Clinical Meetings 2024 (#448).