Blood Pressure Control in Patients with IgAN on Ravulizumab: Prespecified Analysis of the Phase 2 SANCTUARY Trial

Background: Changes in blood pressure could be associated with changes in protein excretion in patients with kidney disease. Ravulizumab (RAV) reduced proteinuria in IgA nephropathy by 30.1% versus placebo at week (wk) 26 of the SANCTUARY clinical trial (NCT04564339), with effects persisting at wk 50.1 The effect of RAV on blood pressure in SANCTUARY has not been previously reported. Methods: SANCTUARY is a randomized, double-blind, placebo-controlled trial of RAV in adults with IgA nephropathy, proteinuria ≥1 g/d, and eGFR ≥30 ml/min per 1.73 m2, and on stable renin-angiotensin blockade with no expected changes in dose during the study. The trial included patients with controlled and stable blood pressure over the past 3 months (systolic blood pressure [SBP] <140 / diastolic blood pressure [DBP] <90 mmHg). Patients were randomized 2:1 to RAV (IV q8 wks) or placebo (PBO) for 26 wks. From wk 26–50, all participants received open-label RAV. Results: N=66 participants were randomized at 38 sites in 11 countries; all but 2 completed study to Wk 50. All participants received either angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) for ≥3 months prior to screening. In the RAV-RAV and PBO-RAV groups, 20 (47%) and 13 (57%), respectively, had a history of hypertension. The mean (SD) baseline SBP and DBP in RAV-RAV (124±11 / 77±8) and PBO-RAV (127±12; 77±9) groups were similar. The average changes in SBP and DBP at wks 26 and 50 were similar between treatment groups (Table 1). Adverse events potentially associated with blood pressure were infrequent and balanced between the groups. Conclusion: Blood pressure was stable among participants in the SANCTUARY trial over time. 1. Lafayette R, et al. J Am Soc Nephrol. 2025;36(4):645–656. Funding: Commercial Support - Alexion, AstraZeneca Rare Disease