Interim findings from the phase III APPLAUSE-IgAN study, presented at the National Kidney Foundation (NKF) Spring Clinical Meeting, indicated that Iptacopan (Fabhalta) is both safe and effective in reducing proteinuria in patients with biopsy-confirmed immunoglobulin A nephropathy (IgAN).

In this study, Iptacopan, when added to supportive care, achieved a 38.3% reduction in the 24-hour urine protein-creatinine ratio (UPCR) at nine months compared to placebo. By the second week of treatment, reductions in UPCR from the first morning void were observed. Over nine months, it declined steadily, resulting in a 35.8% relative reduction between the Iptacopan and placebo groups.

The findings highlighted that Iptacopan is the first potential treatment for IgAN targeting the alternative complement pathway. The interim results were based on data from 250 patients who reached the nine-month mark or discontinued treatment. The primary efficacy analysis focused on patients with an estimated glomerular filtration rate (eGFR) of ≥30 mL/min/1.73 m² and a UPCR of ≥1 g/g at baseline. 

All participants had been on maximally tolerated renin-angiotensin system (RAS) inhibitors for at least three months before the study. Those randomized to Iptacopan received 200 mg twice daily. Nearly all patients were on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, with 12.8% stable on an SGLT2 inhibitor.

By the nine-month mark, twice as many patients on Iptacopan achieved a 24-hour UPCR under 1 g/g compared to the placebo group (42.5% vs. 21.9%). Additionally, no patients in either group required kidney replacement therapy during the trial, although 1.6% of those on Iptacopan and 8% of those on placebo-initiated alternative or rescue medications. 

The study also reported a significant increase in the proportion of patients with negative or trace dipstick hematuria on Iptacopan, which more than doubled from 19.2% to 46% by month nine while remaining relatively stable in the placebo group (25% to 32.7%).

(Source:https://www.medpagetoday.com/meetingcoverage/nkf/110167 )