Evaluating Efgartigimod in Patients With Primary Immune Thrombocytopenia

Treatment with the neonatal Fc receptor antagonist efgartigimod led to clinically relevant increases in platelet counts in patients with primary immune thrombocytopenia (ITP), according to results from a small phase II trial published in the American Journal of Hematology. Treatment also was associated with lower bleeding rates, the authors, led by Adrian C. Newland, MD, from the Centre for Haematology at The Royal London Hospital, wrote.

“IgG autoantibodies directed against platelet receptors can be detected [in most patients with ITP]. They accelerate platelet clearance and destruction, inhibit platelet production, and impair platelet function, resulting in increased risk of bleeding and impaired quality of life,” Dr. Newland and co-authors explained. “Efgartigimod is a human IgG1 antibody Fc-fragment, a natural ligand of the neonatal Fc receptor (FcRn), that blocks FcRn, preventing IgG recycling, and causing targeted IgG degradation.”

In this randomized, double-blind, placebo-controlled trial, the investigators evaluated the safety and efficacy of this novel agent in 38 patients with primary ITP. People with a total IgG level <6 g/L at screening were excluded from the analysis.

Patients were randomized 1:1:1 to receive 4 weekly intravenous infusions of placebo (n=12) or efgartigimod 5 mg/kg (n=13) or 10 mg/kg (n=13).

Baseline characteristics were “generally comparable” across the treatment groups, the authors reported. The median age was 41 years (range = 19-77), most participants had chronic ITP that lasted longer than 12 months (74%), and 20 patients (53%) had a baseline platelet count <15×109/L. Patients were permitted to be on concurrent ITP therapy during the study but had to be on a stable dose and dosing frequency for ≥4 weeks prior to screening. Corticosteroids were the most common prior treatment (84%), followed by thrombopoietin receptor agonists (37%).

Overall, 35 (92%) patients completed the treatment period. Investigators observed that efgartigimod at either dose induced a rapid reduction of total IgG levels. From baseline to 3 days after the fourth infusion, efgartigimod-treated patients in the 5 mg/kg group experienced a mean maximum change of 60% group while those in the 10 mg/kg group experienced 64% decrease. However, IgG levels in the placebo group remained unchanged.

These reductions were associated with clinically relevant increases in platelet counts, with both efgartigimod-treated groups achieved a higher mean maximum platelet count change from baseline compared with the placebo group.

For example, 7 patients in each of the efgartigimod-treated groups (54% for each) achieved a platelet count of ≥50×109/L at any time, compared with 6 patients (50%) in the placebo group. A deeper platelet response (count ≥100×109/L at any time) was achieved by 6 patients (46%) in the efgartigimod 5 mg/kg group, 5 (39%) in the efgartigimod 10 mg/kg group, and 1 (8%) in the placebo group.

Furthermore, 5 patients (39%) in the efgartigimod 5 mg/kg group and 5 patients (39%) in the efgartigimod 10 mg/kg group met the criteria for response according to the International Working Group (defined as platelet count ≥30×109/L and <100×109/L, and at least doubling of baseline platelet count confirmed on ≥2 separate consecutive occasions ≥7 days apart, and the absence of bleeding). Only 2 patients in the placebo group reached this endpoint.

The investigators also performed post hoc analyses to further characterize the magnitude and duration of effect of efgartigimod. The mean cumulative duration of platelet count ≥50×109/L was 24.5 days, ranging between 3 and 73 days for efgartigimod-treated patients; for placebo-treated patients, the duration was 7.3 days, ranging between 4 and 9 days.

“Most patients who responded to efgartigimod had a transient increase in platelet counts, with counts returning to baseline levels in the treatment-free follow-up period,” the researchers noted. However, 2 patients with newly diagnosed ITP and 1 with chronic ITP remained in remission throughout the follow-up period (up to 162 days).

Efgartigimod was well tolerated, with no dose-related safety observations and a safety profile that was consistent with earlier studies, the authors reported. During the study period, 9 patients (69%) treated with efgartigimod 5 mg/kg, 11 (85%) with efgartigimod 10 mg/kg, and 7 (58%) with placebo experienced ≥1 treatment-emergent adverse event (AE), most of which were mild or moderate in severity. The most common AEs among efgartigimod-treated participants were:

  • hematoma (23% with 5 mg/kg and 15% with 10 mg/kg)
  • petechiae (15% in each group)
  • purpura (15% with 5 mg/kg and 8% with 10 mg/kg)

One (8%) patient treated with efgartigimod at 10 mg/kg experienced worsening ITP, which led to drug discontinuation; however, this was considered unlikely related to study drug.

Bleeding symptoms also were reduced with efgartigimod treatment: The proportion of patients with bleeding decreased from 46.% at baseline to a minimum of 8% (1 patient) at day 64 in the 5 mg/kg group, and from 38% at baseline to a minimum of 8% at day 29, in the 10 mg/kg group. In the placebo group, the reduction was less substantial (from 33% at baseline to 25% at day 50).

“The observation that efgartigimod increases platelet counts in patients with ITP predominantly refractory to previous lines of ITP therapy, regardless of prior use of ITP therapies, … supports the central role of pathogenic IgGs in ITP and potential utility of IgG depletion,” the investigators concluded.

However, the study’s findings are limited by the small number of enrolled patients. In addition, “the treatment intervention was short, making efficacy analyses challenging and undermining assessment of the duration of effect and potential utility as chronic treatment,” the authors added.

The authors report relationships with argenx, which sponsored the trial.


Newland AC, Sánchez-González B, Rejtő L, et al. Phase 2 study of efgartigimod, a novel FcRn antagonist, in adult patients with primary immune thrombocytopenia. Am J Hematol. 2020;95:178-187.