Low Bleeding Rates with Increase or Maintenance of Physical Activity in Patients Treated with Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in the A-LONG and Kids A-LONG Studies

Background: The phase 3 A-LONG and Kids A-LONG studies demonstrated low annualized bleeding rates (ABRs) with reduced infusion frequency rFVIIIFc prophylaxis 1-2 times/week in adults, adolescents, and children with severe hemophilia A. Median prestudy and on-study total weekly prophylactic factor consumption was comparable for subjects previously receiving FVIII prophylaxis.

Aims: To evaluate the effect of rFVIIIFc on subjects' physical activity across age groups using a subject-reported assessment and examine ABRs according to change in physical activity and prestudy treatment regimen (prophylaxis or episodic) in A-LONG and Kids A-LONG.

Methods: Previously treated males with severe haemophilia A (<1 IU/dL endogenous FVIII activity) were eligible for A-LONG (≥ 12 years of age) and Kids A-LONG (<12 years of age). A-LONG enrolled subjects into 1 of 3 arms: Arm 1, individualized prophylaxis; Arm 2, weekly prophylaxis; or Arm 3, episodic treatment. All subjects in Kids A-LONG received rFVIIIFc prophylaxis. There were no restrictions on physical activity in either study. Physical activity assessments were conducted at Weeks 7, 14, 28, 38, and 52 (A-LONG) and Weeks 2, 7, 12, 17, 22, and 26 (Kids A-LONG). At each visit after their first rFVIIIFc dose, subjects were asked to report their activity levels relative to their prior study visit as: more (or more intensive), fewer (or less intensive), or about the same amount of activity. To summarize changes in physical activity throughout the study versus baseline, subjects were classified into 1 of 4 groups: more, same, less, or undetermined. Within treatment groups, prestudy and on-study ABRs were analyzed according to change in physical activity category and prestudy regimen. Analyses included all subjects who received ≥ 1 dose of rFVIIIFc during the efficacy period and who completed ≥ 1 physical activity assessment.

Results: This analysis included 163 subjects from A-LONG and 69 subjects from Kids A-LONG. The majority of subjects in both studies reported more or the same amount of physical activity; few subjects reported less physical activity (more, same, less, undetermined): A-LONG Arm 1 (n = 117), 51%, 36%, 8%, 5%; Arm 2 (n = 23), 39%, 48%, 9%, 4%; Arm 3 (n = 23), 26%, 52%, 9%, 13%; and Kids A-LONG (n = 69), 61%, 26%, 6%, 7%, respectively. Similar physical activity results were observed in subjects with target joints at baseline. Median ABRs were lower with rFVIIIFc prophylaxis in A-LONG for all categories of change in physical activity, regardless of prestudy regimen (Table). In Kids A-LONG subjects on prestudy prophylaxis who reported more or similar physical activity, median ABRs with rFVIIIFc were similar or lower than prestudy ABRs.

Summary/Conclusion: The majority of subjects in A-LONG (86%) and Kids A-LONG (87%) reported maintained or increased physical activity levels on-study, with low ABRs. These results suggest that people with severe hemophilia A across age groups may maintain or increase physical activity levels with rFVIIIFc while maintaining low bleeding rates with reduced infusion frequency.