Efgartigimod for Immune Thrombocytopenic Purpura

Efgartigimod is an investigational, neonatal Fc antibody fragment that targets the neonatal Fc receptor and competitively inhibits binding and, consequently, recycling of IgG antibodies (both pathogenic and nonpathogenic), leading to a significant reduction in IgG antibody half-life. IgG autoantibodies against platelet surface glycoproteins are a main driver of immune thrombocytopenic purpura (ITP) pathogenesis. In a prior phase 2 study, efgartigimod was associated with a clinically relevant improvement in platelet counts versus placebo in patients with ITP (Am J Hematol 2020; 95:178).

Now, investigators report an industry-funded, international, phase 3 study (ADVANCE IV) of efgartigimod in 131 patients with ITP. At baseline, patients had a mean platelet count of 16.3×10⁹/L and a mean disease duration of 10.6 years; 67% had received ≥3 prior ITP treatments, and 50% were receiving concurrent ITP therapy. Patients were randomized 2:1 to receive intravenous efgartigimod (10 mg/kg) or placebo for 4 weeks, followed by weekly or every-other-week infusions for up to 14 weeks, based on platelet response.

The primary endpoint of a sustained platelet count of ≥50×10⁹/L for at least 4 of 6 weeks during weeks 19 through 24 — evaluated in the 90% patients with chronic disease (lasting >12 months) — was improved with efgartigimod versus placebo (22% vs. 5%; P=0.032), as was duration of disease control (median 2.0 vs. 0.0 weeks; P=0.0009). Adverse events were comparable between treatment groups; most were mild or moderate. No serious infections were reported.