Background/Purpose: Background: BDCA2 is a plasmacytoid dendritic cell (pDC)-specific receptor that, when ligated inhibits the production of inflammatory mediators and Type I Interferon (INF), a major player in  Systemic and Cutaneous Lupus Erythemtosus’s (SLE and CLE) pathogenesis. Targeting BDCA2 with BIIB059, a high affinity humanized IgG1 mAb, represents an attractive therapeutic strategy. BIIB059 was previously tested in a Phase 1 study in non-Japanese healthy volunteers (HV) (NCT02106897)* and is currently in phase 2 development for the treatment of SLE and Cutaneous Lupus Erythematosus (CLE) (NCT02847598) .  

Methods: Methods: A total of 32 HV from Japanese descend matched for body weight (NCT02106897), were enrolled into 4 cohorts to receive a single subcutaneous (SC) injection of  20-, 50-, 150- or 450 mg of BIIB059 or placebo (6 BIIB059: 2 Placebo). Blood samples were obtained to characterize PK and PD profiles and establish PK-PD relationships for BIIB059. Safety and tolerability data were monitored and reviewed.

Results: Results: BIIB059 was generally well tolerated; no SAEs were observed. Adverse events were reported by 9 (37.5%) and 0 (0.0%) subjects in the BIIB059- and placebo-treated groups, respectively. Overall, 33.3% and 4.2% subjects reported AEs that were mild or moderate in severity, respectively. Three subjects (12.5%) experienced AEs considered related to study drug and mild in severity. All AEs resolved without treatment. There were no clinically significant findings on laboratory measures or in physical examination. Following single SC BIIB059 administration, Cmax and AUC(0-inf) increased with doses. Mean t1/2 ranged from 10 to 27 days. A PK and PD comparison between non-japanese and japanese HV is being conducted and results will be presented here.  Eleven subjects (45.8%) treated with BIIB059 tested positive for anti-BIIB059 antibodies at ≥ 1 postdose timepoint (ADA). There was no apparent relationship between incidence of ADA and dose, no apparent effect on drug exposure and no association with clinically relevant observations. Following BIIB059 administration, BDCA2 expression on pDCs sharply decreased with levels returning towards baseline in a dose-dependent manner as serum concentrations of BIIB059 decreased.

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Conclusion: Conclusions:

• BIIB059 was generally well tolerated.
• BIIB059 exposure increased with dose.
• Preliminary results suggest no apparent PK/PD and safety differences between body weight matched Japanese and Non-Japanese healthy subjects at all doses after single BIIB059 administration.      
• BDCA2 expression on pDCs decreased rapidly and sharply and returned to baseline levels in a dose‑dependent manner.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-tolerability-pharmacokinetic-and-pharmacodynamic-effect-of-biib059-a-monoclonal-antibody-targeting-bdca2-following-administration-of-subcutaneous-single-doses-in-japanese-healthy-volunters/