Table 2.
Efficacy endpoints of completed and interim-reported clinical trials of BAFF/APRIL-targeted biologics for IgAN, LN, and pMN, by standardized time frame.
| Time frame | Biologics | Disease | Endpoint time | Proteinuria reduction | eGFR change | Immunological endpoints |
|---|---|---|---|---|---|---|
| short-term (≤24–28 weeks) | Sibeprenlimab NCT03719443 | IgAN | 16–24 weeks | Not reported | Not reported | IgA −57.2%, IgG −33.6%, IgM −67.2%, and Gd-IgA1 −71.6% at Week 12. |
| Telitacicept NCT04291781 | IgAN | 24 weeks | 24-h proteinuria −49%(240 mg) and −25%(160 mg). | eGFR: +2.34 (240 mg) and +4.32 (160 mg) mL/min/1.73 m2 vs. –5.70 (placebo) | IgA fell ∼46%, IgG ∼25%, IgM ∼65%. Gd-IgA1 −43.9%/−50.4% (160/240 mg). | |
| Atacicept NCT02808429 | IgAN | 24 weeks | 24-h UPCR median change from baseline: placebo +24%; atacicept 25 mg −24%; atacicept 75 mg −25%. | Median change from baseline in eGFR: placebo −7%; atacicept 25 mg −7%; atacicept 75 mg −4%. | IgA: placebo +4%; atacicept 25 mg −13%; atacicept 75 mg −52%. IgG: −8%; −10%; −31%. IgM: −4%; −38%; −69%. Gd-IgA1: +2%; −25%; −60%. | |
| Belimumab NCT01610492 | pMN | 28 weeks | UPCR: −31%(geomean 724→498 mg/mmol). | Stable eGFR overall. | PLA2R:-Ab: 73% reduction from baseline; geomean decreased from 168 RU/mL to 46 RU/mL). | |
| mid-term (36–52 weeks) | Sibeprenlimab NCT04287985 | IgAN | 12 months | 24-h UPCR: −47.2%/58.8%/62.0% (2/4/8 mg/kg) vs. −20.0% placebo. | Annualized eGFR slope: –4.1, +0.1, –0.8 mL/min/1.73 m2/year vs. –5.9 placebo. | Gd-IgA1 and IgA reduced by ∼65%, IgG by ∼35%, and IgM by ∼75%. |
| Sibeprenlimab NCT05248646 | IgAN | 9–12 months | 24-h UPCR:−50.2% (sibeprenlimab) vs. +2.1% (placebo) at 9 months; −56.6% vs. −5.1% at 12 months. | Not reported | Gd-IgA1 −67.1%, APRIL −95.8%, IgA −68.8%, IgG −35.0%, IgM −74.5%. | |
| Telitacicept NCT05799287 | IgAN | 39 weeks | 24-h UPCR: −58.9%(telitacicept) vs. −8.8%(placebo); Proteinuria response (UPCR <0.8): 61.0% vs. 19.5% with placebo. | eGFR stable (telitacicept) vs. ↓(placebo). Confirmed ≥30% eGFR: −6.3% vs. −27.0%. | CD19+ B-cell counts decreased by 46.4% with telitacicept (vs. +4.5% with placebo). Serum IgA fell by 60.6%. | |
| Atacicept NCT04716231 | IgAN | 36 weeks | 24-h UPCR: −45.7% (atacicept) vs. −6.8% (placebo); UACR −47.3% vs. −8.8% (placebo). | eGFR slope results not reported in this interim analysis. | Galactose-deficient IgA1 decreased by 68.3% with atacicept vs. 2.9% with placebo. | |
| Povetacicept NCT05732402 | IgAN | 48 weeks | 24-h UPCR: −64% (80 mg) vs. −56%(240 mg) | .Mean eGFR change: +3.3 mL/min/1.73 m2 (80 mg) and +3.2 mL/min/1.73 m2 (240 mg); annualized eGFR slope not reported. | Early Gd-IgA1 reductions at Week 12: –57% (80 mg), –59% (240 mg); deepened to –77% in both cohorts by Week 48. | |
| Belimumab NCT02260934 | LN | 48 weeks | Complete renal response: 38% (RCB) vs. 32% (RC). Partial renal response: 14% vs. 9%. Overall renal response (complete + partial): 52% vs. 41%(p = 0.452). |
ANA + naive B cells decreased from baseline in 8/9 RCB participants vs. increased in 5/7 RC participants (p = 0.0349). | ||
| Atacicept NCT00573157 |
LN | 52weeks | Not reported | Not reported | 3 patients: IgG < 3 g/L (protocol discontinuation threshold) | |
| Povetacicept NCT05732402 |
pMN | 48 weeks | 24-h UPCR: −82% (3.8→0.7 g/g). Baseline UPCR ≥3.5 g/g (n = 6): −85%. Overall clinical remission: 100% (5/5); | Stable eGFR: mean change –0.3 mL/min/1.73 m2. In the subset with baseline UPCR ≥3.5 g/g: eGFR change +2.2 mL/min/1.73 m2. | aPLA2R −73% (W12), −83% (W48; 98% in nephrotic subset). Immunologic remission (aPLA2R < 14 RU/mL): 100% at W48. | |
| long-term (≥100 weeks) | Blisibimod NCT02062684 |
IgAN | 168 weeks | 24-h UTP: Slight fluctuation initially, marked decline later (Blisibimod); Stable early, continuous increase after mid-term (placebo). | Annualized eGFR slope(mL/min/1.73 m2/year): +6.2 with blisibimod vs. –4.8 with placebo. | Serum immunoglobulins (IgA, IgG, IgM) showed marked reductions throughout treatment. |
| Zigakibart NCT03945318 |
IgAN | 100 weeks | 24-h UPCR: −60.4%(Zigakibart). | Annualized eGFR slope: +0.48 mL/min/1.73 m2/year. | IgA −74.3% (W 100), Gd-IgA1 −74% (W 76), IgM −80% (Week 100), IgG −36%. | |
| Belimumab NCT01639339 |
LN | 104 weeks | Primary efficacy renal response: 43% (belimumab) vs. 32% (placebo). Complete renal response: 30% vs. 20%. Partial renal response: 18% vs. 17%. |
Not reported | ||
UPCR, urine protein-to-creatinine ratio; eGFR, estimated glomerular filtration rate; W, week; UP, urine protein; TEAE, treatment-emergent adverse event; AEs, adverse events; SAEs, serious adverse events; Unit conversion, UPCR 1 mg/mmol ≈ 0.00884 g/g.