Overview of Clinical Trials With Efgartigimod in Autoimmune Blistering Diseases: Pemphigus Vulgaris and Pemphigus Foliaceus (ADDRESS and ADDRESS+) and Bullous Pemphigoid (BALLAD and BALLAD+)

Abstract

Introduction & Objectives: Efgartigimod is an engineered Fc fragment that inhibits the activity of the neonatal Fc receptor (FcRn), thereby reducing levels of circulating IgG including pathogenic IgG autoantibodies. Pemphigus vulgaris (PV), pemphigus foliaceus (PF), and bullous pemphigoid (BP) are autoimmune blistering diseases. Pemphigus is mediated by IgG autoantibodies targeting desmoglein (Dsg)-3 in PV, and Dsg-1 in mucocutaneous PV (in addition to Dsg-3), while PF is attributed to IgG autoantibodies against Dsg-1 only. Dsg-3 and Dsg-1 are desmosomal proteins mediating keratinocyte cell-cell adhesion. BP is mediated by IgG autoantibodies against BP180 (type XVII collagen) and BP230 structural proteins of the dermal-epidermal junction. Materials & Methods: ADDRESS is a multicenter, randomized, double-blind, placebo-controlled trial evaluating efficacy and safety of efgartigimod in patients with PV or PF (NCT04598451). Participants are undergoing randomization (2:1) to receive subcutaneous efgartigimod co-formulated with PH20 or placebo/PH20 on top of oral prednisone (or equivalent). Primary endpoint is the proportion of patients with PV or PF who achieve complete remission on minimal therapy (CRmin) within 30 weeks. BALLAD is a global, multicenter, phase 2/3, randomized, double-blind, placebo-controlled trial evaluating efficacy and safety of subcutaneously administered efgartigimod in patients with BP (NCT05267600). Part A will be a proof-of-concept study and recruit 40 participants, while the Part B confirmatory study will recruit 120 participants. Parts A and B will be identical in schedule, structure, assessments, and conduct. Primary endpoint is the proportion of participants in complete remission off oral corticosteroid therapy for ≥8 weeks at week 36. Results & Conclusions: As of February 28, 2023, 222 participants have been enrolled into ADDRESS and enrolment of BALLAD has started. It is anticipated that the recruitment of the ADDRESS full study and BALLAD part A will be completed, and a further update will be given at the time of presentation.