Efficacy and Safety of Subcutaneous Efgartigimod PH20 in Adults With Primary Immune Thrombocytopenia (ADVANCE SC): A Multicenter, Randomized, Double-Blinded, Placebo-Controlled, Phase 3 Trial.

Primary autoimmune thrombocytopenia (ITP) is characterized by thrombocytopenia, bleeding, and reduced health-related quality of life. In the Phase 3 ADVANCE IV study, intravenous efgartigimod induced significant platelet count responses versus placebo in patients with chronic ITP. ADVANCE SC, a Phase 3, multicenter, randomized, double-blinded, placebo-controlled, parallel-group study, evaluated the efficacy and safety of subcutaneous efgartigimod PH20 in adults with primary ITP. Participants with platelet counts < 30 × 109/L who received more than one prior ITP therapy. Between December 16, 2020, and October 9, 2023, 207 participants were randomized (2:1) to receive 1000 mg efgartigimod PH20 SC (n = 137) or placebo (n = 70) once weekly (visits 1-4), weekly or biweekly (depending upon response; visits 5-16), and at a fixed dosing interval (visits 17-24). Most (92.8% [192/207]) had chronic ITP and 74.9% (155/207) received at least three previous ITP treatments. The median time since diagnosis was 7.0 years. Superior efficacy of efgartigimod PH20 SC versus placebo was not demonstrated for the primary or secondary endpoints, with a comparable proportion of efgartigimod PH20 SC and placebo-treated participants achieving the primary efficacy endpoint (platelet count ≥ 50 × 109/L for at least four of the six visits during weeks 19-24): -13.7% [17/124] versus 16.2% [11/68], respectively; p = 0.51; adjusted difference in proportions, -3.5% [95% CI, -14.7-7.0]. Efgartigimod PH20 SC was well tolerated: most adverse events were mild to moderate and comparable between treatment groups. Platelet count increases from baseline were higher than expected with placebo and lower than expected with efgartigimod PH20 SC. Clinical Trial Registration: The ADVANCE SC trial is registered on ClinicalTrials.gov (NCT04687072).