S302: long-term safety and efficacy of efgartigimod in patients with primary immune thrombocytopenia: interim results of the advance+ study

Background: Efgartigimod (EFG) is a first-in-class human IgG1 antibody Fc fragment that reduces total serum IgG levels, including pathogenic IgG autoantibodies, through neonatal Fc receptor blockade. Primary immune thrombocytopenia (ITP) is an autoimmune disorder mediated by antiplatelet autoantibodies, resulting in thrombocytopenia, bleeding, and constitutional symptoms. ADVANCE, a phase 3 study in 131 adults with long-standing ITP (mean time since diagnosis 10.6 years), including those who received multiple prior ITP therapies, has reported positive efficacy and safety results.1 At treatment period completion, participants were eligible to enroll in the open-label extension (OLE) study, ADVANCE+. Aims: Long-term safety and efficacy of EFG in adults with primary ITP in ADVANCE+. Methods: ADVANCE+ is a 52-week OLE of ADVANCE, extendable up to 3 additional 52-week periods. EFG (10 mg/kg IV) is continued weekly or every other week as per ADVANCE. The dosing regimen may be adjusted to platelet count response. Concurrent ITP therapy may be reduced or stopped at the investigator’s discretion when platelet count is >100×109/L. The primary endpoint is the frequency and severity of adverse events (AEs), as well as vital signs and laboratory assessments. Efficacy endpoints, including platelet count response and bleeding events, are also assessed. Due to the nature of the underlying disease, bleeding events were considered AEs of special interest. Results: As of September 2022, 101 participants entered ADVANCE+. Twenty-seven (26.7%) participants have completed the first 52 weeks of the study, 46 (45.5%) are still ongoing, and 51 (50.5%) have discontinued the study [lack of efficacy n=23, consent withdrawn (not related to a TEAE) n=20, physicians’ decision n=4, death n=3, and other n=1]. The investigator did not consider any AEs leading to death related to EFG. Mean (SD) number of EFG administrations was 26.8 (18.89); 31 (30.7%) received every-other-week dosing at any time up to week 24. Most commonly reported AEs (≥10% of participants) were microscopic blood present in urine (n=42, 41.6%), COVID-19 (n=20, 19.8%), and petechiae (n=17, 16.8%); most were mild or moderately severe. Infections were mostly mild or moderately severe and occurred in 34 (33.7%) participants. 58.8% of participants with an infection experienced COVID-19; other infections included influenza, nasopharyngitis, upper respiratory tract infection, urinary tract infection, pulpitis dental and rhinitis. Of 38 participants who received placebo in ADVANCE, 10 (26.3%) had sustained platelet count responses (platelet count of ≥50 × 109/L during ≥4 of 6 visits between weeks 19 and 24 without intercurrent events) and 9 (23.7%) had a platelet count ≥50×109/L for at least 4 of the first 6 weeks. The mean (SE) percentage of weeks with a platelet count of ≥50×109/L was 39.2% (3.86). Sustained reductions of ~60% from baseline in total serum IgG were observed. Of the 41 evaluable participants receiving concurrent therapy at baseline, 4 (9.8%) reduced concurrent ITP therapy during the first 52-week treatment period. Summary/Conclusion: These interim analyses suggest long-term continued EFG treatment in participants with long-standing ITP including those who have received multiple prior therapies was well tolerated and not associated with an increased exposure-adjusted risk for infection. Sustained reductions in total IgG levels and platelet count increases (Figure 1) were also observed. Participants who switched from placebo to EFG had early platelet count increase, which generally mirrored participants who received EFG in ADVANCE.Keywords: Autoimmune disease, Chronic ITP, Autoimmunity