Atacicept kept eGFR stable for a year in IgA nephropathy

Design

Phase 3, randomised, double-blind, placebo-controlled trial (final efficacy analysis)

Population

428 adults with biopsy-confirmed IgA nephropathy

Primary outcome

eGFR change at 52 weeks and annual eGFR slope to 104 weeks

Effect

eGFR difference 5.58 mL/min/1.73 m² (95% CI 3.68–7.48); kidney progression HR 0.24 (0.12–0.48)

ORIGIN 3 randomised 428 adults with biopsy-confirmed IgA nephropathy to weekly subcutaneous atacicept 150 mg or placebo. An earlier analysis showed a fall in proteinuria; these are the final kidney function results.

At 52 weeks eGFR had changed by −0.11 mL/min/1.73 m² on atacicept and −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 versus −5.60. Composite kidney progression occurred in 5.1% versus 17.8% (HR 0.24, 95% CI 0.12–0.48); no one on atacicept progressed to dialysis, transplantation or death, against seven on placebo. Serious adverse events were less common on atacicept (7.0% vs 15.4%).

Atacicept blocks two B-cell survival signals, BAFF and APRIL, which drive production of the abnormal IgA. For a non-nephrologist, the point is that IgA nephropathy — common, often found on a routine urine dipstick in young adults — is moving from a disease managed with blood pressure control towards one with targeted therapy. Its regulatory status and availability in India are not yet clear.

• Refer young adults with persistent microscopic haematuria and proteinuria for assessment, as IgA nephropathy is a common cause
• Keep maximising RAS blockade and blood pressure control — that remains the base of treatment
• Expect nephrologists to discuss B-cell–targeted therapies for patients with persistent proteinuria
• Atacicept's licensing and availability in India are unknown at present

Why it matters

IgA nephropathy is shifting from a watch-and-wait disease to one where early referral changes options.

Don't overread it

The eGFR outcomes were secondary end points and two-year follow-up is short for a disease that progresses over decades.

The statistics, in plain English

A hazard ratio of 0.24 means kidney progression occurred at about a quarter of the rate seen on placebo. The eGFR slope difference of 5 mL/min per year is large: untreated patients here were losing kidney function about ten times faster.

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