Introduction Hemophilia A is a rare, genetic bleeding disorder that leads to recurrent hemarthrosis, causing debilitating pain and joint deterioration, and ultimately results in reduced mobility and a poor quality of life. The aim of this study was to gain insight into caregivers' perspectives on the impact of hemophilia and its treatment as well as experiences with efanesoctocog alfa prophylaxis, by conducting optional qualitative exit interviews with caregivers of children with severe hemophilia A exiting the XTEND-Kids study. Methods XTEND-Kids (NCT04759131) was a Phase 3, open-label, multicenter study evaluating the safety, efficacy, and pharmacokinetics of once-weekly efanesoctocog alfa (50 IU/kg) for 52 weeks, in previously treated children aged <12 years with severe hemophilia A. Semi-structured exit interviews were conducted with caregivers of children from 12 clinical sites across four countries (Canada, France, United Kingdom, and the United States) at their 52-week end-of-treatment (EOT) visit and before end-of-study (EOS) was declared. All caregivers of children across these countries were given the option of participating in the exit interviews. In addition to open-ended questions about the caregiver and their child's experience with hemophilia A, more targeted questions relating to hemophilia-related symptoms and experience with treatments before and during the XTEND-Kids study were queried (Yes/No; Likert Scale). Interviews were conducted by experienced moderators in each country's native language using translated guides where applicable and lasted approximately 60 minutes. Interviews were audio recorded and transcribed for analysis. Descriptive statistics of select items from the qualitative data were computed and summarized. Results Seventy-two children completed their Week 52 EOT or EOS visit; 19 caregivers (18 mothers; 1 father) of 20 children completed exit interviews (one caregiver was the parent of two children in the study). Mean (SD) age of the children was 6.5 (3.1) years, and all were male. All children were receiving FVIII replacement prophylaxis prior to study entry, except for one in the 6 to <12 years of age cohort who was receiving an on-demand regimen. Regarding pre-study treatment experiences, nine caregivers (47.4%) reported that their child's bleeds had a negative impact on their own day-to-day life and eight caregivers (42.1%) reported their child's bleeds had a negative impact on their own mood and emotions . According to caregivers, the most significant impact of hemophilia A and its treatment on their children was on mood and emotions (n=19/20 children; 95.0%) and their physical health/activity (n=14/20 children; 70.0%). When queried about what bothered their children most about their hemophilia and its treatment pre-study, caregivers reported that six children were most bothered about being more cautious or less active than other children due to their condition and 12 children were most bothered about the number of treatment infusions per week. In the XTEND-Kids study, all caregivers (n=19; 100%) reported at least one improvement in their child as a result of efanesoctocog alfa prophylaxis, with eight caregivers (40.0%) stating their child had longer or better protection due to higher factor levels. All caregivers (n=19; 100%) reported noticing a positive effect on their child's daily life and functioning, with most caregivers (n=18; 94.7%) reporting that treatment with efanesoctocog alfa had improved their child's mood and emotions (Figure 1). Efanesoctocog alfa prophylaxis also led to positive changes in caregivers' daily life and functioning, with improvements (out of those who reported the impact at baseline) seen by caregivers in managing treatment (n=16; 100%), impact on family (n=11; 100%), mood/emotions (n=15; 93.8%), and work (n=11; 91.7%) (Figure 2). All caregivers (n=19; 100%) preferred efanesoctocog alfa over their children's previous hemophilia treatment; 18 (94.7%) were “very satisfied”, with one (5.3%) caregiver “satisfied”. Conclusion Caregivers of children with severe hemophilia A reported major impacts at study baseline on both daily life and functioning with prior treatments. Efanesoctocog alfa prophylaxis provided improvements in both children and their caregiver's daily life and functioning, and all caregivers preferred efanesoctocog alfa to their child's previous treatment.