070 Treating Bullous Pemphigoid by Inhibiting FcRn: A Phase 2/3 Trial with Efgartigimod

Abstract

Efgartigimod (EFG) is an engineered Fc fragment that inhibits the activity of the neonatal Fc receptor (FcRn), thereby reducing the levels of circulating immunoglobulin G (IgG), including pathogenic IgG autoantibody, levels. EFG is clinically efficacious and generally well tolerated in phase 2 and 3 trials in multiple IgG-mediated disorders. Bullous pemphigoid (BP) is an autoimmune blistering disease, characterized by subepidermal blisters and mediated by IgG autoantibodies against BP180 (type XVII collagen) and BP230, structural proteins of the dermal-epidermal junction. Administration of an EFG analogue prior to and after that of pathogenic anti-BP180 IgG antibodies in a BP mouse model demonstrated efficacy in reducing skin disease activity. EFG will be evaluated as a therapy for BP in BALLAD, a phase 2/3 randomized, double-blinded, placebo-controlled trial (NCT05267600). BALLAD will be conducted in two parts – a proof-of-concept Part A (N=40) and a confirmatory Part B (N=120). Both parts are identical in schedule, structure, assessments, and conduct. 2000 mg EFG PH20 SC will be given on days 1 and 8, and 1000 mg EFG PH20 SC will be given weekly through week 35. Oral corticosteroids starting at 0.5 mg/kg/day of prednisone will be administered to the EFG PH20 SC and placebo PH20 SC groups and adjusted to each participant’s disease status. The primary endpoint is the proportion of participants in complete remission on minimal oral corticosteroid therapy (≤0.1 mg/kg/day) for ≥8 weeks at week 26. Key secondary endpoints include cumulative dose of oral corticosteroids from day 1 to week 36, change in the Bullous Pemphigoid Disease Area Index (BPDAI) score, incidence and severity of adverse events, and quality of life scores.