PB0630 - Final Analysis of Long-term Clinical Outcomes of Prophylaxis With a Recombinant Factor VIII Fc Fusion Protein in Adults Aged ≥50 Years With Severe Hemophilia A

Background: A-LONG (NCT01181128) and ASPIRE extension (NCT01454739) Phase 3 studies evaluated efmoroctocog alfa (a recombinant factor VIII Fc fusion protein; referred to herein as rFVIIIFc) in previously treated subjects with severe hemophilia A (SHA).

Aims: Post hoc analysis of final data from subjects aged ≥50 years with SHA in A-LONG/ASPIRE.

Methods: Treatment groups in ASPIRE included individualized prophylaxis (IP; rFVIIIFc 25–65 IU/kg every 3–5 days), weekly prophylaxis (WP; 65 IU/kg every 7 days), modified prophylaxis (MP; more tailored dosing), and on-demand treatment (bleed-dependent dosing). Outcomes included annualized bleed rate (ABR), ABRs for subjects with target joints, hemophilia quality of life questionnaire for adults (Haem-A-QoL), modified hemophilia joint health score (mHJHS), factor consumption, and cumulative exposure. Subjects provided informed consent.

Results: Twenty-one subjects ≥50 (median [range], 57 [50–65]) years enrolled in A-LONG and/or ASPIRE. Median (interquartile range [IQR]) duration of rFVIIIFc treatment was 4.3 (3.1–5.4) years, encompassing a median (IQR) of 318 (257–425) rFVIIIFc exposure days. At baseline, 10/21 subjects (48%) had ≥1 documented comorbidity and 13/21 subjects (62%) were receiving ≥1 concomitant medication (Table). rFVIIIFc prophylaxis in older subjects with SHA resulted in low overall and joint ABRs (Figure). All 42 evaluable target joints resolved during prophylaxis. No subject developed inhibitors. Factor consumption was relatively stable in subjects on prophylaxis from the end of A-LONG to the end of ASPIRE. Mean (standard deviation) change in total Haem-A-QoL score and mHJHS from A-LONG baseline to last available assessment in ASPIRE was −2.13 (12.11) and −8.40 (10.87), respectively, in subjects who were always on rFVIIIFc prophylaxis.

Conclusion(s): rFVIIIFc prophylaxis over ~4 years resulted in low ABRs, improved joint health, and stable factor consumption for previously treated subjects with SHA ≥50 years, suggesting clinical benefit of rFVIIIFc in this subgroup. Data are consistent with the overall study population.

Funded by Sanofi and Sobi.