Real-World Use of Efanesoctocog Alfa in Adult Patients with Hemophilia a Including Those with a History of Factor VIII Inhibitor

Introduction: Efanesoctocog alpha (Efa), a factor VIII replacement therapy independent of von Willebrand factor, is approved for patients with hemophilia A (PwHA). The goal of this study was to report “real world” post-licensure experience treating a diverse group of patients with Efa, performing modified pharmacokinetics (PK), and obtaining estimated treatment cost analysis.

Methods: We performed a retrospective review of adult PwHA who received Efa at the UC Davis Hemostasis Thrombosis Center February 2023-June 2024. Approval was obtained by institutional IRB. Data included patient demographics, severity of hemophilia, bleeding events, current therapy and Factor VIII inhibitor history.

Efa start date, dose, dosing interval, and factor VIII PK values were obtained. Factor VIII levels were measured using an adjusted in-house assay or commercial Labcorp test (chromogenic Factor VIII was used for one patient). For PwHA on prophylaxis pre/post financial analysis was done to assess whether changes in therapy led to differences in costs. Costs were based on Wholesale Acquisition Cost (WAC) and 340B pricing data from our institution for therapy prior to and including Efa, calculated per unit using an exact weight-based dose. Annual cost projections were based on a regimen maintained over one year, respective to each patient's dose interval.

Results: Twenty-five PwHA were screened, 24 included in final analysis. The mean age of PwHA was 41.7 years (range 25-75 years old), 40% self-identified as non-Hispanic white, Hispanic (24%), Asian (16%), and Black/African American (8%). Five PwHA had moderate and 19 had severe HA. Five PwHa had history of Factor VIII inhibitor. Eighteen PwHA used extended half-life recombinant Factor VIII products, one used standard half life products, and four used emicizumab-kxwh. One patient had no prior treatment records. Four PwHA were treated on demand. For PwHA on prophylaxis, Efa was prescribed weekly according to package insert. Nineteen PwHA underwent the first Efa infusion in clinic, five self-infused at home. Twenty-four PwHA obtained peak PK values within 24 hours following initial infusion of Efa (mean Factor VIII activity 135.8%, SD 36.7%). One transitioned from prophylactic emicizumab to Efa, and PK values were obtained using chromogenic Factor VIII assays (peak 113.8% and Day 7 10.3%). In the days following infusion, two PwHA collected troughs on Day 6 (16.3-39.2%, mean 27.8%), 15 PwHA collected troughs on Day 7 (mean 11.2%, SD 10.3%), and two PwHA collected troughs on Day 8 (6.3-10.0%, mean 8.2%). Five patients had no trough collected. Four PwHA with a history of Factor VIII inhibitors treated with tolerization in childhood had no significant difference in factor peak (mean 163.8%; SD 18.5%) or trough (mean 15.7%, SD 20.9%). One PwHA had a history of high-titer inhibitor treated with immune tolerization therapy in childhood had profoundly low trough of 2% on Day 7. Two PwHA experienced bleeding while on Efa, one with gastrointestinal bleeding and one intraarticular shoulder bleed. One PwHA experienced an infusion reaction after the fourth dose and one developed vasovagal syncope after the first dose; the drug was discontinued in both subjects.

The average annual cost difference for PwHA who switched to Efa was increased by $121,542 compared to their prior therapy under 340B pricing ($198,614 under WAC pricing).

Conclusions: This is one of the largest real-world studies of Efa that includes a diverse group of adult patients with moderate to severe hemophilia A, some of whom have a history of Factor VIII inhibitor. PK values, when accounting for interlaboratory differences, are comparable with the initial phase 3 study, and real-world measurement is feasible even outside of a clinical trial. Performing PK may be particularly informative in patients with history of high titer inhibitors. Few drug-related adverse events were reported.

Treatment with Efa was on average more expensive than prior therapies. Our cost analysis is based on estimates, actual costs may differ. Future studies should aim to evaluate long-term comprehensive outcomes in patients on Efa prophylaxis and its impact on health care system utilization.

Giermasz:ATHN: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; BioMarin: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees; uniQure: Honoraria, Membership on an entity's Board of Directors or advisory committees.