Effect of Efgartigimod IV on Immature Platelet Count Fraction in Primary Immune Thrombocytopenia

Immature platelet fraction (IPF%) is the number of immature platelets (PLT) relative to total PLT number and is a measure for enhanced PLT degradation. IPF% is increased in patients with primary immune thrombocytopenia (ITP) and in some countries, such as Japan, it is used as part of the ITP diagnostic criteria. ITP is a bleeding disorder caused by accelerated PLT destruction and impaired production facilitated in part by autoantibodies. Efgartigimod is a human IgG Fc fragment engineered to bind competitively to the neonatal Fc receptor (FcRn) with high affinity, preventing endogenous IgG recycling and reducing IgG levels, including pathogenic IgG autoantibodies. In 2024, intravenous (IV) efgartigimod was approved for the treatment of patients with chronic primary ITP in Japan.

Efficacy and safety of efgartigimod IV were evaluated in ADVANCE IV (NCT04188379), a phase 3, multicenter, double-blinded, placebo-controlled trial in adults with persistent and chronic primary ITP. Participants with an average of 2 PLT counts <30×10⁹/L during screening were randomized to efgartigimod IV 10 mg/kg or placebo. Primary endpoint was the proportion of chronic ITP participants with a sustained PLT count response (defined as PLT counts of at least 50×10⁹/L for at least 4 of the 6 visits between Weeks 19 and 24 of the study). IPF% was also measured as exploratory research to evaluate the effects of efgartigimod on PLT turnover. IPF% was measured locally in facilities equipped with a hematology analyzer that could determine this platelet subset.

In ITP participants (N=131), sustained PLT response was demonstrated in more efgartigimod IV-treated participants (25.6%) than placebo (6.7%; P=0.0108). In the 40 participants of which immature platelets were measured, mean [±SE] IPF% was reduced following efgartigimod IV treatment (baseline IPF%, 21.6 [±2.6]; Week 24 IPF%, 13.6 [±2.7]) while no decrease was noted for placebo (baseline IPF%, 29.2 [±5.3]; Week 24 IPF%, 33.8 [±4.5]).

Observed PLT count responses in efgartigimod IV-treated participants with primary ITP are likely mediated by a reduction in PLT degradation.

Matthijssens:argenx: Current Employment, Current holder of stock options in a privately-held company, Patents & Royalties. Miyakawa:argenx: Consultancy, Honoraria; UCB: Consultancy, Research Funding; Zenyaku: Consultancy; Alexion: Research Funding; BioMarin: Research Funding; Chugai: Research Funding; CSL Behring: Research Funding; Janssen: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisc: Research Funding; Pfizer: Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Asahi Kasei: Honoraria. Nishiwaki:Janssen Pharmaceutical K.K.: Honoraria; Chugai Pharmaceutical CO., LTD.: Honoraria; Nippon Shinyaku CO., LTD.: Honoraria; Alexion Pharmaceuticals, Inc.: Honoraria; Abbvie Inc.: Honoraria; Pfizer Inc.: Honoraria. Ayguasanosa:argenx: Current Employment, Current equity holder in publicly-traded company. Lan:argenx: Current Employment, Current holder of stock options in a privately-held company. Hultberg:argenx: Current Employment, Current holder of stock options in a privately-held company, Patents & Royalties. Ulrichts:argenx: Current Employment, Current holder of stock options in a privately-held company.

As of 2024, efgartigimod is approved for use in patients with primary immune thrombocytopenia (ITP) in Japan but not currently approved by the FDA or EMA. Since efgartigimod, a human IgG1 fragment, is a natural ligand of FcRn, it prevents recycling of endogenous IgG antibodies, including anti-platelet autoantibodies in the case of primary ITP. The ADVANCE IV trial (NCT04188379) investigated intravenous efgartigimod across patients with ITP, demonstrating significantly increased sustained platelet count responses compared with placebo, including those who had received multiple previous ITP therapies. This analysis aimed to investigate the mechanism behind these platelet count responses using measurements of the participants immature platelet fraction (defined as the number of immature platelets relative to total platelet number) as an indicator for enhanced platelet degradation.