Principia Biopharma Inc. announced positive data from its Phase 2 Part B open-label trial in pemphigus, BELIEVE-PV. The full data set was presented as part of the virtual Late-Breaker session of the American Academy of Dermatology. The significance of this Phase 2 Part B trial is that rilzabrutinib, a reversible covalent oral BTK inhibitor, demonstrated a 40% complete remission (CR) rate after 24 weeks of treatment while the median corticosteroid (CS) dose was reduced to 6 mg. Among the 15 patients with newly diagnosed/relapsed, mild-to-severe pemphigus in this trial, a clinically meaningful decrease in the daily CS use was observed -- the median CS dose was 18 mg/day (0.201 mg/kg/day) at baseline and in the 14 patients that completed 12 and 24 weeks of treatment the median CS dose decreased to 11 mg/day (0.125 mg/kg/day) at 12 weeks and decreased again to 6 mg/day (0.076 mg/kg/day) at 24 weeks. All treatment related adverse events with rilzabrutinib were mild-to-moderate (including grade 1 and 2 nausea, abdominal distension, and dizziness), consistent with the Phase 2 Part A trial. An oral therapy such as rilzabrutinib has the potential to benefit patients with pemphigus in multiple ways, including rapid anti-inflammatory effects, neutralization of effects of autoantibodies, and blockage of the production of new autoantibodies, while not depleting B cells. About PEGASUS -- the Phase 3 Trial of Rilzabrutinib: Principia is currently enrolling patients in a global, randomized, double-blind, placebo-controlled, pivotal, Phase 3 clinical trial, the PEGASUS study, in approximately 120 participants to evaluate rilzabrutinib versus placebo, using a background treatment of tapering doses of corticosteroids (CS). The trial entry criteria include participants with moderate to severe pemphigus who are either newly diagnosed or relapsing with chronic disease. This demographic will potentially represent three quarters of the pemphigus patient population. The primary efficacy endpoint is the ability of rilzabrutinib to achieve durable complete remission (CR) after 36 weeks of treatment. Durable CR is defined as a state in which all lesions have healed on very low dose CS (5mg/day), and no new lesions have appeared for a period of at least eight weeks. Key secondary endpoints include cumulative CS use and time to CR. After 36 weeks, all patients will have the option be treated with active rilzabrutinib therapy in an open-label extension period of 24 weeks. Rilzabrutinib has been granted orphan drug designation by the U.S. Food and Drug Administration for the treatment of patients with pemphigus vulgaris (PV) and by the European Commission for treatment of patients with PV and pemphigus foliaceus.