Treatment of pemphigus vulgaris and foliaceus with efgartigimod, a neonatal Fc receptor inhibitor: a phase 2 multicentre, open-label feasibility trial

BACKGROUND Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoimmune disorders triggered by immunoglobulin G (IgG) autoantibodies against mucosal and epidermal desmogleins. There is an unmet need for fast-acting drugs that enable patients to achieve early sustained remission with reduced corticosteroid reliance. OBJECTIVE To investigate efgartigimod, an engineered Fc fragment that inhibits the activity of the neonatal Fc receptor, thereby reducing serum IgG levels, for treating pemphigus. METHODS Thirty-four patients with mild to moderate pemphigus vulgaris or foliaceus were enrolled in an open-label phase 2 adaptive trial. In sequential cohorts, efgartigimod was dosed at 10 or 25 mg/kg intravenously with various dosing frequencies, as monotherapy or as add-on therapy to low-dose oral prednisone. Safety endpoints comprised the primary outcome. RESULTS Adverse events were mostly mild and reported by 16/19 (84%) patients receiving efgartigimod 10 mg/kg and 13/15 (87%) patients receiving the 25 mg/kg dose, with similar adverse event profiles between dose groups. A major decrease in serum total IgG and anti-desmoglein (Dsg) autoantibodies was observed and correlated with improved pemphigus disease area index (PDAI) scores. Efgartigimod, as monotherapy or combined with prednisone, demonstrated early disease control in 28/31 (90%) patients after a median of 17 days. Optimized, prolonged treatment with efgartigimod in combination with a median dose of 0.26 (range 0.06-0.48) mg/kg/day prednisone led to complete clinical remission in 14/22 (64%) patients within 2-41 weeks. CONCLUSION Efgartigimod was well-tolerated and exhibited an early effect on disease activity and outcome parameters, providing support for further evaluation as a therapy for pemphigus. The study is registered at ClinicalTrials.gov (identifier: NCT03334058).