Boom or Bust: Clinical Trials in Pemphigus and Other B-Cell–Mediated Autoimmune Diseases

Abstract

Pemphigus vulgaris (PV) is a B-cell–mediated autoimmune blistering disease characterized by autoantibodies targeting skin cell adhesion proteins. Despite the well-defined pathophysiology and unmet need for safe and effective therapies for pemphigus, multiple therapeutics have failed to advance through clinical development. Prednisone and rituximab are clinically approved for PV, but the neonatal Fc receptor inhibitor efgartigimod and Bruton’s tyrosine kinase inhibitor rilzabrutinib failed to receive clinical approval in pemphigus, despite success in other autoantibody-mediated diseases. Conversely, the success of rituximab for PV has not been reproduced for several other B cell–mediated autoimmune diseases. We review learnings from the successes and failures of rituximab, efgartigimod, and rilzabrutinib across B-cell–mediated autoimmune diseases and compare trial designs and endpoints to identify key issues affecting clinical outcomes.