APPLAUSE-IgAN: Landmark Phase III Results for Iptacopan

Novartis reported that the Phase III APPLAUSE-IgAN trial showed iptacopan (Fabhalta) met its primary endpoint, slowing the eGFR slope over two years versus placebo.

The trial's primary endpoint was the annualized eGFR slope measured over a 24‑month treatment period — a validated marker of progressive kidney function loss and a direct indicator of long‑term renal prognosis. The final analysis signaled a favorable direction of effect across the trial population, consistent with disease‑modifying activity rather than a transient biomarker shift. The two‑year horizon aligns with accepted regulatory and clinical frameworks for assessing chronic kidney disease progression.

Iptacopan is an oral Factor B inhibitor that targets the alternative complement pathway, reducing complement‑mediated glomerular injury that contributes to IgA nephropathy. Unlike supportive measures alone, this targeted mechanism aims to interrupt a biologic driver of inflammation and proteinuria. Supportive care — including RAAS blockade and SGLT2 inhibition where used — remains foundational and can be continued alongside complement inhibition when indicated. Taken together, the mechanism and Phase III efficacy data support iptacopan as a new targeted option for progressive IgAN.

Novartis plans to use the APPLAUSE‑IgAN dataset as the backbone of traditional regulatory submissions expected in 2026, with the Phase III eGFR‑slope result forming the core efficacy narrative for dossiers. Because a two‑year slope endpoint maps to clinical progression, it will likely shape regulatory discussions on benefit magnitude and the overall risk‑benefit assessment. A positive regulatory decision would shorten the path from pivotal readout to broader availability and payer engagement, materially affecting development and access timelines for the program.