Atacicept held kidney function steady over two years in IgA nephropathy

Design

Phase 3, randomised, double-blind, placebo-controlled; final efficacy analysis

Population

428 treated adults with biopsy-confirmed IgA nephropathy

Primary outcome

eGFR change at 52 weeks and annualised eGFR slope to 104 weeks (secondary end points)

Effect

Slope −0.60 vs −5.60 per year (difference 5.00, 95% CI 3.55–6.45); progression HR 0.24

ORIGIN 3 randomised 431 adults with biopsy-proven IgA nephropathy to weekly subcutaneous atacicept 150 mg or placebo. Atacicept blocks two cytokines that drive B cells to make the abnormal IgA behind the disease. An earlier report showed it lowered proteinuria; this final analysis looks at kidney function itself.

At one year, eGFR was essentially unchanged on atacicept (−0.11 mL/min/1.73 m²) and fell by 5.69 on placebo, a difference of 5.58 (95% CI 3.68–7.48). Over two years the annual eGFR slope was −0.60 on atacicept against −5.60 on placebo. A composite of kidney-disease progression occurred in 5.1% versus 17.8% (HR 0.24, 0.12–0.48). Seven placebo patients and no atacicept patients reached dialysis, transplant or death. Serious adverse events were less frequent with atacicept (7.0% vs 15.4%).

The same week brought interim or final phase 3 reports of three other agents aimed at the same pathway in IgA nephropathy. For a non-nephrologist the message is that a disease many once watched with only blood pressure control and RAS blockade is acquiring disease-modifying options. Eligibility, cost and regulatory status in India are not established in the candidate record.

The trial was funded by the manufacturer, and eGFR outcomes were secondary end points tested in a hierarchy.

• Refer adults with haematuria and proteinuria for nephrology review; IgA nephropathy is the commonest primary glomerulonephritis worldwide.
• Do not accept slow eGFR decline in young adults as inevitable; disease-specific treatment is arriving.
• Keep blood pressure control and RAS blockade in place; new agents add to supportive care, not replace it.
• Hard outcomes such as dialysis were few in two years; longer follow-up will show whether the eGFR gain lasts.

Why it matters

It moves IgA nephropathy from a disease managed supportively to one where progression may be modifiable.

Don't overread it

eGFR change is a surrogate; with two years of follow-up, the trial cannot yet show fewer people reaching dialysis.

The statistics, in plain English

An eGFR slope difference of 5.0 mL/min/1.73 m² per year means kidney function was being lost about 5 units a year more slowly — large relative to the placebo decline. A hazard ratio of 0.24 means composite progression was about three-quarters less frequent, with a confidence interval (0.12 to 0.48) well clear of 1.0.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.