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Efgartigimod safe and effective for primary immune thrombocytopenia

In the phase III ADVANCE trial, efgartigimod, a human immunoglobulin (Ig) G1 Fc-fragment, showed an early platelet count increase and higher sustained platelet count response compared with placebo among patients with immune thrombocytopenia (ITP).

Primary Immune Thrombocytopenia (ITP) is an acquired autoimmune disorder in which immunoglobulin G (IgG) platelet autoantibodies accelerate platelet clearance and impair platelet production. The disease is thus characterised by a reduction in platelet count, which can result in an increased risk of bleeding, fatigue and decreased quality of life (QoL). As current treatment options can be associated with comorbidities, unsatisfactory efficacy and duration of effect and have only a limited impact on QoL measures, there is a need for better ITP therapy. Efgartigimod  is a human IgG1 Fc-fragment that competitively inhibits the neonatal Fc receptor, preventing IgG to bind. As such, it prevents the recycling of endogenous IgG, thereby reducing IgG levels including IgG autoantibody levels. The efficacy and safety of intravenous (IV) efgartigimod was evaluated in ADVANCE, a phase III, multicentre, randomised, double-blinded, placebo-controlled trial in adults with persistent or chronic ITP.

Study design

Participants with an average of two platelet counts (PLTs) below 30×109/L during screening were randomised 2:1 to receive 10 mg/kg EFG or placebo for 24 weeks. Concurrent oral corticosteroids, oral immunosuppressants, dapsone, danazol, fostamatinib, and oral thrombopoietin receptor agonists (not romiplostim) were permitted but required to remain at the entry dosage and frequency. Participants received weekly dosing (weeks 1–4) followed by response-dependent weekly or every 2 weeks (Q2W) dosing (weeks 5–16) and then maintained their dosing regimen from weeks 17–24. The primary and key secondary endpoints were tested in hierarchical order. The primary endpoint was the proportion of chronic ITP participants with a sustained PLT response (PLT of ≥50×109/L in at least 4 of 6 visits between weeks 19 and 24 without intercurrent events. Key secondary endpoints included extent of disease control (cumulative weeks with PLTs of ≥50×109/L) in the chronic population, proportion of participants in the overall population (chronic and persistent) with sustained PLT response, incidence of bleeding events, and a durable sustained platelet response (PLT of ≥50×109/L in ≥6 of 8 visits between weeks 17 and 24) in the overall population. Safety and pharmacodynamic measures were also evaluated.


In total, 131 patients were randomised to efgartigimod (N= 86) or placebo (N= 45). Most patients had chronic ITP (N= 118), others had persistent ITP. In the efgartigimod arm, participants had long-standing, severe ITP (median time since diagnosis of 10.3 years; baseline median PLT of 17.3×109/L) and were heavily pretreated (68.6% had ≥3 prior ITP therapies). Efgartigimod demonstrated early sustained increases in platelet counts. In total, 33 patients (38.4%) treated with efgartigimod as compared to 5 patients (11.1%) treated with placebo reached a platelet count of 30x109 platelets at week 1. Moreover, a sustained platelet count response was achieved in 90% (9/10) of participants who switched from weekly to every other week dosing, indicating that there is some flexibility in dosing schedule possible. The benefit of efgartigimod was consistent across all subgroups analysed, regardless of age, sex, severity of disease, time since diagnosis, prior ITP treatment or background medication.

Efgartigimod was well-tolerated in patients with ITP and consistent with other efgartigimod studies. Treatment-emergent adverse events (TEAEs) were reported in 93.0% of participants in the efgartigimod group and 95.6% in the placebo group. Serious TEAEs were reported in 8.1% of participants in the efgartigimod group and in 15.6% in the placebo group, and none were treatment related. These included bleeding or events related to bleeding (N= 5), infections (N= 4), and worsening primary ITP (N= 3). No deaths or increased risk of infection were observed.


The benefits of targeting FcRn and lowering total IgG levels were demonstrated by clinically and statistically significant improvements in platelet counts compared with placebo. Efgartigimod was well tolerated and most adverse events were mild to moderate with no new safety signals. The results of the study support both weekly and every-other-week administration, allowing for adjustments based on platelet counts.


Broome C, et al. Efficacy and Safety of Intravenous Efgartigimod in Adults with Primary Immune Thrombocytopenia: Results of a Phase 3, Multicenter, Double-Blinded, Placebo-Controlled, Randomized Clinical Trial (ADVANCE IV). Presented at ASH 2022; Abstract 3.

Speaker Catherine Broome

Catherine Broome

Catherine Broome, MD, Georgetown University, Washington DC, USA


See: Keyslides


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