EFFICACY AND SAFETY OF IPTACOPAN IN PATIENTS WITH IGA NEPHROPATHY (IGAN): INTERIM ANALYSIS (IA) OF THE PHASE 3 APPLAUSE-IGAN STUDY

Introduction:

There is growing evidence for involvement of the alternative complement pathway in IgAN pathogenesis. No currently approved therapies specifically target this pathway.

Methods:

APPLAUSE-IgAN (NCT04578834) is a Phase 3, randomized, double-blind, placebo-controlled study of iptacopan on top of optimized supportive care in patients with biopsy-confirmed IgAN and proteinuria ≥1 g/g by UPCR from 24h urine collection (UPCR-24h) despite maximally tolerated RAS inhibition for ≥3 months. Patients were randomized 1:1 to iptacopan 200 mg or placebo twice daily.

Results:

Efficacy analyses at the pre-specified IA included 125 patients each for iptacopan and placebo; safety analyses included 222 and 221 patients, respectively. Baseline characteristics were balanced across treatment arms. Iptacopan was superior to placebo in reducing UPCR-24h from baseline at
Month 9: 38.3% (95% CI 26.0%‒48.6%; 1-sided p<0.0001) reduction relative to placebo. UPCR from first morning void decreased as early as Week 2 and continued to decrease to Month 9: 35.8% (95% CI 22.6%‒46.7%) reduction relative to placebo at Month 9 (Figure). Approximately twice as many patients on iptacopan reached UPCR-24h <1 g/g at Month 9 vs placebo (marginal proportion 42.5% [95% CI 34.5%‒50.5%] vs 21.9% [95% CI 14.8%‒29.0%], respectively). Iptacopan was well tolerated (treatment was discontinued due to AEs in 2.7% patients in each arm) and the infection rate in the iptacopan arm did not exceed that of placebo.

Conclusions:

APPLAUSE-IgAN demonstrated superiority of iptacopan vs placebo in proteinuria reduction at Month 9, with early onset and consistency of effect. Iptacopan was well tolerated with a favorable safety profile.

This abstract was also submitted for the National Kidney Foundation Spring Clinical Meetings,14–18 May 2024, Long Beach, CA, USA.

I have potential conflict of interest to disclose.
Dana V. Rizk reports grants (paid to institution) from Reata Pharmaceuticals, Otsuka Pharmaceuticals, Chinook Pharmaceuticals, LaRoche, Vera Therapeutics, and Vertex Pharmaceuticals, consulting fees from Vera Therapeutics, consulting fees for steering committee participation from Novartis, Otsuka Pharmaceuticals, Chinook Pharmaceuticals, and LaRoche, payments for educational events from Calliditas Therapeutics and Travere Therapeutics, payments for advisory boards or Alpine Immune Sciences, GSK, Biocryst, and Argenx, and support for attending meetings and/or travel from Otsuka Pharmaceuticals.

I did not use generative AI and AI-assisted technologies in the writing process.