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Atrasentan shows positive interim results in IgA nephropathy: ALIGN phase 3 trial

Presented by
Prof. Hiddo J.L. Heerspink, University Medical Center Groningen, The Netherlands
ERA 2024
Phase 3, ALIGN
The endothelin A receptor antagonist atrasentan improves 24-hour proteinuria with favourable safety in IgA nephropathy, according to the ALIGN phase 3 trial.

For the ongoing, randomised, double-blind, controlled ALIGN trial (NCT04573478), adult participants were randomised 1:1 to 132 weeks of atrasentan versus placebo. Participants had a biopsy-proven IgA nephropathy, received renin-angiotensin system inhibitors, and showed a total urine protein ≥1 g/day and an eGFR ≥30 mL/min/1.73 m2. The primary endpoint was 24h urine protein-creatinine ratio at week 36. This interim analysis was presented by Prof. Hiddo J.L. Heerspink (University Medical Center Groningen, The Netherlands) and included 135 participants receiving atrasentan and 135 participants with placebo [1].

Following 36 weeks of treatment, atrasentan significantly reduced proteinuria characterised by 24h urine protein-creatinine ratio (mean change -38.1% vs -3.1%; -36.1% difference; 95% CI -44.6 to -26.7; P<0.0001) compared to placebo. Differences in proteinuria were seen from week 6 onwards and were maintained through week 36. No change in proteinuria was seen with the placebo. A sensitivity analysis taking into account prohibited medication use (immunosuppressants or SGLT2 inhibitors), chronic dialysis, or kidney transplant showed results consistent with the primary analysis. Adverse events more commonly reported with atrasentan were nasopharyngitis, peripheral oedema, fluid retention, vasodilation/hypotension, anaemia and pyrexia. Overall, 5.9% of participants with atrasentan and 6.5% of participants with placebo had serious adverse events. 3.5% of participants in each group discontinued treatment due to adverse events.

“Atrasentan was well-tolerated, has a favourable safety profile, and was superior to placebo in reducing proteinuria at week 36, the primary pre-specified endpoint of the phase 3 global ALIGN trial”, concluded Prof. Heerspink. The ALIGN trial is ongoing and the final results of the primary analysis of eGFR are awaited.

  1. Hiddo JL Heerspink, et al. ALIGN Phase 3 primary endpoint analysis: atrasentan shows significant reduction in proteinuria in patients with IgA nephropathy. Abstract #109, ERA 2024, 23–26 May, Stockholm, Sweden.

Medical writing support was provided by Mihai Surducan, PhD.

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