Phase III Results for Efgartigimod in Primary Immune Thrombocytopenia

“Efgartigimod significantly increased sustained platelet count responses compared with placebo in patients with chronic immune thrombocytopenia, including those who had received multiple previous immune thrombocytopenia therapies,” according to authors of the ADVANCE IV trial, led by Catherine M. Broome, MD, of the Lombardi Cancer Center at Georgetown University in Washington, DC.

The report, published in The Lancet, explained that efgartigimod is a novel first-in-class immunoglobulin G1 (IgG1) Fc fragment that binds to the neonatal Fc receptor in order to reduce serum autoantibodies and other IgG concentrations.

The 24-week, phase III, double-blinded, randomized, controlled trial took place across 71 centers in Asia, Europe, and North America. Eligible participants were aged 18 years or older with chronic or persistent primary immune thrombocytopenia, an average platelet count of less than 30,000, a response to at least one prior immune thrombocytopenia therapy, and either concurrent treatment at baseline or at least a second prior therapy.

Efgartigimod Promisingly Separated From Placebo in ADVANCE IV

Ultimately, the trial randomized 131 patients to either efgartigimod (n=86) or placebo (n=45). The cohort had a mean time since diagnosis of 10.6 years, and 67.0% (n=88) had received three or more prior immune thrombocytopenia treatments.

Researchers administered placebo or efgartigimod 10 mg/kg intravenously for the first four weeks, after which dosing could be modified to once per week or every other week depending on platelet counts. The primary endpoint was sustained platelet count response, defined as a count of ≥50 × 10⁹ for at least four of the final six weeks.

After the intervention period, 17 of 78 patients in the efgartigimod cohort achieved the primary endpoint compared with two of 40 placebo patients (adjusted between-group response difference, 16%; 95% CI, 2.6-26.4; P=.032). The median duration of disease control was two weeks (interquartile range [IQR], 0.0-11.0) with efgartigimod versus zero weeks (IQR, 0.0-1.0) with placebo (P=.0009).

Authors reported efgartigimod was well tolerated and most adverse events (AEs) were mild or moderate. The most common AEs in both the efgartigimod and placebo groups were headache in 15% and 13%, hematuria in 16% and 16%, and petechiae in 15% and 27% of patients, respectively.

An open-label extension study enrolling patients who completed ADVANCE IV is ongoing, and Dr. Broome and colleagues added that “subcutaneous efgartigimod is currently being evaluated in patients with immune thrombocytopenia in the ADVANCE SC+ trial.”

Reference

Broome CM, McDonald V, Miyakawa Y, et al. 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. Lancet. 2023. doi:10.1016/S0140-6736(23)01460-5

Related: Diagnosing and Treating Immune Thrombocytopenic Purpura