Efficacy and safety of the neonatal Fc receptor inhibitor efgartigimod in adults with primary immune thrombocytopenia (ADVANCE IV): a multicentre, randomised, placebo-controlled, phase 3 trial
Phase III study (n=131) found the first-in-class novel human IgG1 Fc fragment increased sustained platelet count responses compared with placebo (22% v 5%; p=0.032) in patients with chronic immune thrombocytopenia, including those who had received multiple previous therapies.
Source:
The Lancet
SPS commentary:
The patient population in this study had a mean time of 10.6 years since diagnosis and 67% had received at least three previous immune thrombocytopenia treatments, including 77 participants (59%) who had received a thrombopoietin receptor agonist and 49 participants (37%) who had undergone splenectomy. Efgartigimod, a decoy Fc fragment that can outcompete endogenous IgG for the neonatal Fc receptor, was administered by once weekly IV infusion for 4 weeks, then every 1-2 weeks depending on platelet count.
The primary endpoint of sustained platelet count response, defined as a platelet count of ≥50 × 109 per L for 4 of the last 6 weeks of follow up, was achieved by a higher proportion of patient randomised to efgartigimod than placebo, with an adjusted difference of 16% (95% CI 2.6–26.4). Despite IgG concentrations decreasing to 60% less than baseline, efgartigimod was well tolerated, with no significant increase in serious infections.
A related comment notes the results were ‘modest’, likely due to the heavily pretreated population. However the observed improvement in platelet count associated with a therapy that targets IgG provides support for the antibody hypothesis to explain the mechanism of immune thrombocytopenia. It is noted that the positioning of efgartigimod in clinical practice is uncertain; it is less convenient that some other treatments due to the need for regular IV infusion, and it is likely to be used in those who have not responded to thrombopoietin receptor agonists. Subcutaneous efgartigimod is currently being evaluated in patients with immune thrombocytopenia in the ADVANCE SC+ trial.