Iptacopan's slowing of eGFR decline in IgA nephropathy was sustained to four years

Design

Open-label rollover extension of the phase 3 APPLAUSE-IgAN trial

Population

368 adults with IgA nephropathy (194 from iptacopan arm, 174 switched from placebo)

Primary outcome

Total eGFR slope and proteinuria over up to 48 months

Effect

eGFR slope −3.49 (−4.17 to −2.80); placebo switchers −5.29 to −2.11 mL/min/1.73 m²/year; UPCR ratio 0.61

APPLAUSE-IgAN showed that iptacopan, an oral factor B inhibitor, slowed eGFR decline over two years. Patients who finished the trial could continue or start iptacopan in an open-label extension.

Those who continued kept a slower rate of decline and lower proteinuria over four years. Those switched from placebo saw their rate of decline more than halve after starting iptacopan.

Without a control group, the extension cannot prove that iptacopan caused the improvement, but the within-patient switch from placebo is a useful signal. Complement inhibition requires vaccination against encapsulated organisms.

• eGFR slope on iptacopan for up to 48 months was −3.5 mL/min/1.73 m² per year.
• Proteinuria remained about 39% below baseline at four years.
• Patients switched from placebo improved their slope from −5.3 to −2.1.
• No new safety signals appeared up to five years.
• Iptacopan requires vaccination against encapsulated bacteria before starting; check local availability and cost in India.

Why it matters

Durability was the main uncertainty after the two-year trial, and these data show the effect holding, including in patients who started late.

Don't overread it

The extension is open-label and uncontrolled after month 24, so patients who stayed in may differ from those who left.

The statistics, in plain English

eGFR slope is the yearly loss of kidney function. Going from −5.3 to −2.1 means losing about 3 mL/min less each year, which over a decade could delay dialysis substantially. Uncontrolled comparisons are weaker than randomised ones.

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