Gazyvaro (obinutuzumab) 1000mg solution for infusion 

REGENCY: a Phase 3, randomised, double-blind clinical trial through 76 weeks to assess the efficacy and safety profile of GAZYVARO® + ST vs. placebo + ST in patients (N=271) with active lupus nephritis. The primary endpoint was the proportion of participants who achieved CRR at Week 76. With GAZYVARO® + ST (n=135), significantly more patients achieved CRR vs. placebo + ST (n=136) at Week 76 (46.4% vs. 33.1%, respectively); treatment difference: 13.4% (95% CI, 2.0 to 24.8; P=0.02). In pooled data from placebo-controlled studies in 200 patients with lupus nephritis treated with GAZYVARO®, the most frequently observed adverse drug reactions were upper respiratory tract infection (29%), COVID‑19 (22.5%) and urinary tract infection (21%). ^{Ref 7}

*ST defined as MMF plus glucocorticoids. ^{Ref 7}

†CRR at Week 76 was defined as UPCR <0.5 g/g; an eGFR ≥85% of baseline, as calculated using the 2009 CKD-EPI equation; with no occurrence of the following intercurrent events: rescue therapy, treatment failure, death, or early study  withdrawal.Treatment failure was defined as ESKD or the use of long-term dialysis or renal transplantation, receipt of rescue therapy (except for glucocorticoid-only rescue),or clinically significant and sustained worsening of the UPCR and/or eGFR beyond Week 24 that led the centre investigator to conclude that the assigned regimen had failed. ⁷

‡A Cochran–Mantel–Haenszel test with the stratification factors of race and geographic region was performed to test the null hypothesis of equal response proportions. The adjusted differences (i.e., the common risk differences) were calculated with the use of Mantel–Haenszel weights. The 95% CIs are based on the standard error obtained from the stratified Newcombe CI with the use of Mantel–Haenszel weights. Patients who discontinued GAZYVARO® or placebo were evaluated with the use of their observed data according to the treatment-policy strategy. ^{Ref 7}

§P<0.05: Testing for statistical significance of the primary and the key secondary endpoints was performed with the use of fixed-sequence testing with a fallback procedure adaptation to control the trialwide type 1 error rate at a 5% significance level. ^{Ref 7}

¶Lupus nephritis flare was defined as eGFR decrease >20% compared with Week 24 in patients with UPCR >1 g/g and/or cellular casts, UPCR increase (one of the following: >1 g/g, if Week 24 UPCR was <0.2 g/g, or >2 g/g, if Week 24 UPCR was 0.2–1 g/g, or double if Week 24 UPCR was >1 g/g), and receipt of rescue therapy, except for glucocorticoid-only rescue. ^{Ref 8}

# Statistical significance cannot be claimed as there was no correction for multiplicity. ^{Ref 8}

** Successful prednisone taper was defined as no receipt of prednisone at a dose higher than 7.5 mg per day from Week 64 through Week 76. ^{Ref 7} 

††4x 1000 mg IV doses during the first year: Dose 1: initial infusion; Dose 2: Week 2 (2 weeks after Dose 1); Dose 3: Week 24; Dose 4: Week 26 (2 weeks after Dose 3); Dose 5: 6 months after Dose 4; followed by IV dosing every 6 months  Thereafter. ^{Ref 1} 

‡‡  Based on pooled safety data from the REGENCY trial (Phase 3 study of 136 patients treated with GAZYVARO + ST consisting of MMF and corticosteroids) and the NOBILITY trial (Phase 2 study of 64 patients treated with GAZYVARO + ST with MMF/mycophenolic acid and corticosteroids) in patients with ISN/RPS 2003 Class III or IV with or without concomitant Class V LN, up to Week 76. Frequencies are defined as very common (≥ 1/10) and  common (≥ 1/100 to < 1/10)^{Ref 1}

§§ Frequency category derived from laboratory values collected as part of routine laboratory monitoring in clinical trials. ^{Ref 1}