Long-term atacicept shows continued benefit in IgA nephropathy

Atacicept continued to show improvement in urine protein-creatinine ratio and eGFR stabilisation in participants with IgA nephropathy in the open-label extension of the recently published phase 2b ORIGIN trial.

Atacicept is a dual inhibitor of B-cell Activating Factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL) investigated in the phase 2b ORIGIN trial (NCT04716231). This multinational, randomised dose-range study randomised participants 1:1:1:1 to 36 weeks of atacicept 25 mg, 75 mg, or 150 mg every week or placebo.  Inclusion criteria were the presence of IgA nephropathy confirmed by kidney biopsy, a high risk of disease progression, eGFR ≥30 mL/min/1.73 m², 24-hour urine protein-creatinine ratio of >75 mg/g or 24-hour total urine protein >75 g, and a stable treatment with renin-angiotensin-aldosterone system inhibitors. As recently published, atacicept met its primary endpoint of 24-hour urine protein-creatinine ratio reduction at week 24 in the 116 randomised and treated participants [1]. Prof. Richard Lafayette (Stanford University, CA, USA) presented the 72-week interim results of the open-label extension of the trial [2].

At 72 weeks, 106 participants had completed the open-label extension. Participants who had switched to atacicept by that time had a mean -59% change from baseline in galactose-deficient IgA1 compared to -62% for participants with continuous atacicept. Furthermore, haematuria decreased in 59% of participants switching to atacicept compared with 81% of participants receiving continuous atacicept treatment. The mean urine protein-creatine ratio decreased by 47% from baseline in participants who switched to atacicept and by 45% in patients receiving continuous atacicept by week 72, and eGFR values stabilised in all participants. Atacicept was well-tolerated during the open-label extension, with only 1 participant discontinuing treatment due to adverse events. There were no signals of increased infections.

“Participants treated with atacicept had consistent and sustained reductions in their galactose-deficient IgA1, haematuria and urine protein-creatine ratio, and they have consistent and stable eGFR”, summarised Prof. Lafayette, adding that participants who switched to atacicept demonstrated similar results. “These data provide strong confidence in the ongoing phase 3 trial.”

 

1. Lafayette R, et al. Kidney Int. 2024;105(6):1306–1315.
2. Lafayette R, et al. Phase 2b ORIGIN study open label extension with atacicept in patients with IgA nephropathy and persistent proteinuria: Week 72 interim analysis. Abstract #812, ERA 2024, 23–26 May, Stockholm, Sweden.

Medical writing support was provided by Mihai Surducan, PhD.

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Posted on 20 June 202424 June 2024