Use of efgartigimod (EFG) was associated with improvements in platelet counts compared with placebo in adult patients with immune thrombocytopenia (ITP), according to study results presented at the 2022 ASH Annual Meeting.

The phase 3, multicenter, randomized, double-blinded, placebo-controlled ADVANCE trial ( Identifier: NCT04188379) evaluated the efficacy and safety of intravenous (IV) EFG in adults with persistent or chronic ITP.

Participants aged ≥18 years with 2 platelet counts (PLTs) of <30 × 109/L at screening were randomly assigned 2:1 to receive 10 mg/kg IV of EFG or placebo for 24 weeks. The patients also had at least 2 previous ITP treatments or 1 previous and 1 concurrent treatment. Concurrent ITP therapy was allowed at a stable dose and frequency throughout.

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The patients received fixed weekly dosing from weeks 1 to 4, which was followed by response-dependent weekly dosing or dosing every 2 weeks (q2w) for weeks 5 to 16, and then a fixed weekly or q2w dosing regimen from weeks 17 to 24.

The primary endpoint was the proportion of patients with chronic ITP who had a sustained PLT response (PLT of ≥50 × 109/L in ≥4 of 6 visits from weeks 19 to 24 without intercurrent events such as rescue therapy at week 12 or later). Secondary endpoints included the extent of disease control in the chronic ITP group, the proportion of patients in the overall population with sustained PLT response, incidence of bleeding events, and a durable sustained platelet response in the overall population. Safety and pharmacodynamic measures also were assessed.

A total of 131 participants (118 with chronic ITP, 13 with persistent ITP) were randomly assigned for the study — 86 received EFG (mean age [SD], 46.9 [16.6] years; 54.7% female), and 45 received placebo (mean [SD] age, 51.7 [17.9] years; 53.3% female). The EFG group had a mean time since diagnosis of 10.3 (12.1) years, vs 11.1 (13.1) in the placebo group. In the EFG group, 68.6% had previous use of ≥3 ITP therapies vs 64.4% in the placebo group.

Among the patients with chronic ITP, a sustained PLT response was achieved in 21.8% (17/78) of the EFG group vs 5.0% (2/40) in the placebo group (P =.0316). All PLT-related secondary endpoints were met with EFG, including mean number of cumulative weeks of disease control (EFG 6.1 [7.66] vs placebo 1.5 [3.23]; P =.0009) and sustained platelet count response (EFG 25.6% vs placebo 6.7%; P =.0108).

Of the EFG group, 33 patients (38.4%) achieved a platelet count of 30 × 109/L at week 1 compared with 5 patients (11.1%) in the placebo group. A sustained platelet count response was achieved by 90% (9/10) of patients who switched from weekly dosing to dosing every other week.

The international working group response (consecutive visits ≥7 days apart with PLTs of ≥30 × 109/L and 2-fold increase from baseline in the absence of bleeding events) was observed in 51.2% (44/86) of patients who received EFG vs 20.0% (9/45) of those who received placebo.

Patients who received EFG had substantially more weeks with disease control throughout the study (10% for EFG vs 0% for placebo at weeks 20-24).

The mean immunoglobulin G levels in patients who received EFG decreased steadily during the first 4 weeks of treatment, after which the mean maximum decreases from baseline remained >60% throughout.

Treatment-emergent adverse events (TEAEs) occurred in 93.0% (80/86) of participants in the EFG group and in 95.6% (43/45) in the placebo group. The most common TEAEs were hematuria, headache, and petechiae. Serious TEAEs were reported in 8.1% (7/86) of participants in the EFG group and in 15.6% (7/45) in the placebo group, and none were treatment related.

“EFG was well tolerated and most adverse events were mild to moderate with no new safety signals,” stated the investigators in their presentation.

Disclosure: This study was funded by argenx. Please see the original reference for a full list of authors’ disclosures.

Broome CM, McDonald V, Miyakawa Y, et al. Efficacy and safety of intravenous efgartigimod in adults with primary immune thrombocytopenia: results of a phase 3, multicenter, double-blinded, placebo-controlled, randomized clinical trial (ADVANCE IV). Presented at ASH 2022. December 10-13, 2022. Abstract 3.