Efficacy and Safety of Ravulizumab in IgAN: Week 50 Results from a Phase 2 Randomized Controlled Trial

Background: In IgA nephropathy (IgAN), terminal complement pathway activation contributes to inflammation and glomerular damage. Early and meaningful reductions in proteinuria were demonstrated with complement C5 inhibitor ravulizumab (RAV) in the phase 2 SANCTUARY trial (NCT04564339) through 26wks; efficacy and safety data through 50wks are presented. Methods: Adults with primary IgAN, proteinuria ≥1 g/d, eGFR ≥30 mL/min/1.73 m2, and on stable/optimal RASi were randomized 2:1 to RAV or placebo (PBO) (IV; q8w) for 26wks. At wk26, PBO group switched to open label RAV (PBO-RAV). Primary endpoint: change in proteinuria at 26wks; secondary endpoints: change in proteinuria and eGFR at 50wks. Safety and PK/PD were assessed. Results: Of 66 randomized patients (pts; RAV n=43; PBO n=23), 64 completed wk50. In RAV and PBO arms, respective baseline (BL) UPCR was 1.7 and 1.8 g/g; BL eGFR was 76.0 and 70.4 mL/min/1.73 m2. At 26wks, a –33.2% treatment effect on UPCR was demonstrated with RAV vs PBO (p=0.0011). At 50wks, RAV pts had a 41.1% reduction from BL in UPCR. PBO-RAV pts had a 43.1% decrease in UPCR from BL (wk0) to wk50 (Figure). Annualized eGFR slope in RAV pts was –1.4 at 26wks and –2.3 at 50wks and in PBO-RAV pts was –6.7 and –4.1 at 26 and 50wks, respectively. The majority of AEs were mild; no serious treatment-related AEs, discontinuations from AEs, or deaths occurred. Conclusion: Treatment with RAV was well-tolerated and demonstrated early and sustained proteinuria reduction through ~1 year, and after wk26 switch from PBO to RAV. Funding: Commercial Support - Alexion, AstraZeneca Rare Disease