Efgartigimod confers rapid improvement in platelet counts in immune thrombocytopenia
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NEW ORLEANS — Efgartigimod demonstrated clinically significant improvement in platelet counts compared with placebo among adults with primary immune thrombocytopenia, results of the phase 3 ADVANCE IV trial showed.
More than half of patients in the study responded to the therapy, according to data presented during the plenary session at ASH Annual Meeting and Exposition.
“People living with immune thrombocytopenia need more treatment options that target the underlying disease biology," Catherine M. Broome, MD, associate professor at Georgetown Lombardi Comprehensive Cancer Center, told Healio. “New therapies such as efgartigimod have the potential to significantly reduce the disease burden for people living with [this disease].”
Background
Primary immune thrombocytopenia is an acquired autoimmune disorder that decreases platelet counts. The condition can cause increased risk for bleeding and fatigue and have a detrimental effect on overall quality of life.
Standard first-line therapies for immune thrombocytopenia include steroids and IV immunoglobulin G.
“One of the greatest frustrations expressed from patients regarding managing their [disease] is the unpredictable response for many to standard first-line therapies,” Broome said. “Many patients [with immune thrombocytopenia] are inadequately controlled on current therapies, so there remains a significant unmet need for additional treatment options with new mechanisms of action.”
Methodology
The multicenter, double-blinded, randomized phase 3 ADVANCE IV trial evaluated the safety and efficacy of efgartigimod (argenx) — a neonatal Fc receptor antagonist — among adults with persistent or chronic primary immune thrombocytopenia.
Investigators randomly assigned patients (n = 131) with an average of two platelet counts of less than 30 × 109/L to receive either efgartigimod dosed at 10 mg/kg (n = 86; mean age, 46.9 ± 16.6 years; 54.7% women) or placebo (n = 45; mean age, 51.7 ± 17.9 years; 53.3% women) for 24 weeks. Study participants received weekly dosing for the first 4 weeks followed by response-dependent dosing every week or 2 weeks from weeks 5 through 16 through study completion.
The proportion of patients with a sustained platelet count response of 50 × 109/L or greater in at least four of six follow-up visits between weeks 19 and 24, without the need for rescue therapy at week 12 or later, served as the study’s primary endpoint.
Secondary endpoints included extent of disease control among those with chronic disease, and proportions of participants with sustained platelet count response and a durable sustained platelet response among the overall population.
Key findings
Thirty-three patients (38.4%) who received efgartigimod reached a platelet count of 30 × 109/L at 1 week compared with five patients (11.1%) who received placebo. This signified early, sustained increases in platelet counts, Broome said.
Investigators also observed sustained elevated platelet count responses among nine of 10 recipients of efgartigimod who switched from weekly to every-other-week dosing.
Efgartigimod induced responses in 44 patients (51.2%), including 24 patients (27.9%) who had a complete response according to International Working Group response criteria, compared with a 20% response rate among those who received placebo.
Broome and colleagues reported a 31.2% (95% CI, 13.8-46) difference in response and 23.5% (95% CI, 10.3-35) difference in complete response between the treatment and placebo groups.
The efgartigimod treatment group also demonstrated substantially longer disease control at every week during the treatment period compared with those who received placebo, the investigators noted.
More than 90% of patients in each group had at least one reported treatment-related adverse event. Investigators noted serious treatment-related adverse events more frequently reported in the placebo group (15.6% vs. 8.1%).
The most common treatment-related adverse events in the efgartigimod group included hematuria (16.3%), headache (16.3%) and petechiae (15.1%).
Bleeding events occurred in 70.9% of patients in the efgartigimod group compared with 86.7% in the placebo group.
Clinical implications
Results of the ADVANCE IV study demonstrated clinically and statistically significant improvements in platelet counts for those who received efgartigimod compared with placebo, Broome noted.
“These results are important because there is a need for new therapies [with novel] mechanisms of action that are central to the pathophysiology of primary immune thrombocytopenia,” Broome told Healio.
“The data show that platelet counts can rapidly improve to clinically meaningful levels following efgartigimod treatment in a proportion of a heavily pretreated patient population,” she added. “We are excited that targeting pathogenic [immunoglobulin G] autoantibodies could represent a potentially new approach to help alleviate the disease burden in this patient community.”
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Broome CM, et al. Abstract 3. Presented at: ASH Annual Meeting and Exposition; Dec. 10-13, 2022; New Orleans.
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