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Efgartigimod Works Well in ADVANCED ITP

December 12, 2022

While quite the tongue twister, efgartigimod is a drug transparent in its impact on platelet counts in persistent or chronic primary immune thrombocytopenia (ITP). Primary ITP is an acquired bleeding disorder mediated by autoimmune destruction of platelets that can lead to life-threatening bleeding and significantly impaired quality of life. The current treatment paradigm relies on immunosuppressants (steroids or rituximab), platelet production stimulants (thrombopoietin receptor agonists), and platelet clearance decoys or inhibitors (intravenous immunoglobulin, fostamatinib, splenectomy, and anti-D globulin). In terms of pathophysiology, the culprit autoantibodies in ITP are predominantly of the IgG class with a predilection for targeting surface glycoproteins on platelets and megakaryocytes.

That’s where efgartigimod, an intravenous antibody that works by binding to the neonatal Fc receptor, fits into the picture. Think back to medical school and recall that the bottom of the Y-shaped IgG antibody is referred to as the Fc region. The neonatal Fc receptor binds this portion of the IgG construct and extends the half-life of the IgG antibody as it protects it from lysosomal degradation by recycling it back into the circulation. By binding to the neonatal Fc receptor and disrupting the interaction between the IgG antibody and the neonatal Fc receptor, efgartigimod reduces IgG antibody levels in ITP. As a first-in-class neonatal Fc receptor antagonist, with a sophisticated design that enables it to outcompete endogenous IgGs for binding to the neonatal Fc receptor, the drug has potential for treating a host of autoimmune disorders and has already received U.S. Food and Drug Administration approval for patients with myasthenia gravis with anti-acetylcholine receptor antibodies.         

At the Plenary Scientific Session, Dr. Catherine M. Broome eloquently presented data from the phase III randomized, double-blind, multicenter ADVANCE IV trial, which demonstrated efficacy of efgartigimod, a first-in-class drug for patients with ITP. The trial randomized 131 participants with chronic or persistent ITP and platelet count less than 30 × 109/L to receive either 10 mg/kg of intravenous efgartigimod or placebo for 24 weeks. The infusion was administered weekly for the first four weeks and subsequently given either weekly or every two weeks depending on response. Patients were allowed to be concurrently maintained on a list of approved medications without changes in dosages or frequency. The primary endpoint was the proportion of chronic ITP patients with a platelet count ≥50×109/L in at least four of six visits between weeks 19 and 24 without the need for rescue therapy at week 12 or later. Secondary endpoints included duration (in weeks) of sustained platelet response greater than 50×109/L, durability of response, and incidence of World Health Organization bleeding events.

Study patients had longstanding, severe ITP (median time since diagnosis of 4.57 years with baseline median platelet count of 17×109/L) and were heavily pretreated (67.2% had ≥3 prior therapies). Among patients with chronic ITP, those who received efgartigimod were more likely to achieve a sustained platelet response compared to placebo-treated patients (21.8% vs. 5.0%, p=0.0316). Additionally, all secondary endpoints favored efgartigimod, including an early sustained increase in platelet count and a greater proportion of treated patients who achieved an International Working Group–defined response. Reflecting the activity of the drug, mean IgG antibody levels in efgartigimod treated patients decreased steadily over the first 4 weeks posttreatment, with a mean maximum reduction of 60 percent from baseline. There were no increased risks of infection or treatmentrelated serious adverse events attributed to the study drug. The most prevalent adverse events included bruising, headache, hematuria, and petechiae.

With ITP in the limelight of the Plenary Scientific Session, efgartigimod provides a novel therapeutic approach for patients with this disorder. Further long-term efficacy and safety data are warranted, though the current data suggest a clear ADVANCEment for chronic or persistent ITP.


Dr. Hermel indicated no relevant conflicts of interest.

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