HEMATOLOGY
CONFERENCE UPDATE

Efanesoctocog alfa offers sustained prophylaxis in severe hemophilia A: Interim analysis of the XTEND-ed LTE study

28 Feb 2026

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STUDY DESIGN

Efanesoctocog alfa is a first-in-class high-sustained factor VIII (FVIII) replacement therapy designed to decouple recombinant FVIII from endogenous von Willebrand factor, providing prolonged FVIII activity.1 The phase 3 XTEND-1 study in adults/adolescents and XTEND-Kids study in children demonstrated that once-weekly efanesoctocog alfa led to highly effective bleed protection, maintaining high-sustained FVIII activity within the normal to near-normal (>40%) range for 4 days in adults/adolescents and 3 days in children, with a favorable safety profile.1

The XTEND-ed study is an ongoing, multicenter, open-label long-term extension (LTE) study that enrolled participants with previously treated severe hemophilia A with endogenous FVIII activity <1IU/dL.1 Participants who completed XTEND-1 (≥12 years) or XTEND-Kids (<12 years) rolled over to arm A of XTEND-ed for once-weekly prophylaxis with 50IU/kg efanesoctocog alfa.1 This third interim analysis of the study was conducted to evaluate the safety and efficacy of efanesoctocog alfa prophylaxis with up to 4 years of follow-up in previously treated patients with severe hemophilia A.1

A total of 217 participants rolled over to XTEND-ed, including 146 adults and adolescents with a median age of 37.0 years and 71 children with a median age of 7.0 years.1 The mean exposure days (EDs) were 156.4 and 103.5 weeks, respectively.1 The primary endpoint was FVIII inhibitor development, with secondary endpoints including annualized bleed rates (ABRs), treatment of bleeding episodes, and safety and tolerability.1

​FINDINGS

Primary endpoint:
  • The primary endpoint was the occurrence of FVIII inhibitor development1
  • After a mean exposure of 156.4 weeks in adults/adolescents and 103.5 weeks in children, no FVIII inhibitor development was observed (95% CI: 0.0-2.5 for adults/adolescents; 95% CI: 0.0-5.1 for children)1
Secondary endpoints:
  • The secondary endpoints were ABRs and treatment of bleeding episodes1
  • Adults and adolescents1
    • Low bleed rates (ABR<1) were maintained with once-weekly efanesoctocog alfa prophylaxis, with an overall mean model-based ABR of 0.60, consistent with the ABR of 0.71 reported in XTEND-1 arm A
    • Corresponding model-based ABRs were 0.20 for spontaneous bleeds, 0.29 for traumatic bleeds, and 0.42 for joint bleeds
    • Across individual 6-month intervals over 36 months, 80.7% of participants experienced no bleeds overall, and 91.7% was free of spontaneous bleeds
    • Zero bleeds were observed in 65.8%, 68.1%, and 78.0% of participants for all bleeds, and in 82.9%, 84.4%, and 91.7% of participants for spontaneous bleeds during day 1-month 12, months 13-24, and months 25-36, respectively
    • Of 252 treated bleeding episodes, 94.0% were resolved with a single efanesoctocog alfa injection
    • Participant-rated responses were excellent or good in 87.8% of bleed treatment episodes
  • Children1
    • Bleeding control remained effective, with an overall model-based ABR of 0.64, consistent with the ABR of 0.61 in XTEND-Kids
    • Corresponding model-based ABRs for spontaneous, traumatic, and joint bleeds were 0.08, 0.44, and 0.31, respectively
    • Across individual 6-month intervals over 24 months, 77.1% of children experienced zero bleeds overall, and 97.7% remained free of spontaneous bleed
    • Zero bleeds were observed in 64.8% and 66.1% of participants for all bleeds, and in 94.4% and 96.8% for spontaneous bleeds during day 1-month 12 and months 13-24, respectively
    • Of 89 treated bleeding episodes, 91.0% were resolved with a single efanesoctocog alfa injection
    • Treatment response was rated excellent or good for 94.1% of bleeding episodes
Safety:
  • Treatment with efanesoctocog alfa was well tolerated in all participants, with no treatment-related serious adverse events (TESAEs) reported1
  • Two adult/adolescents experienced treatment-related adverse event (TEAEs), including facial paralysis and reduced FVIII levels, with complete resolution of all events1
  • Three adult/adolescent participants discontinued treatment due to TEAEs unrelated to the study drug1
  • Two children experienced TEAEs, including asthma, post-infusion pain and headache, with all treatment-related events resolved1
  • No treatment discontinuations were reported in the children cohort1

 

“Once weekly efanesoctocog alfa is well tolerated and highly effective in managing severe hemophilia A across all age groups with sustained low ABR, high proportions of zero spontaneous bleeds, and no FVIII inhibitor development.”

Dr. Lynn Malec
Versiti Blood Research Institute,
Milwaukee, United States

​

References

  1. Malec L, et al. Clinical outcomes up to 4 years of once-weekly efanesoctocog alfa prophylaxis in previously treated adults, adolescents, and children with severe hemophilia A: Interim analysis of the Phase 3 XTEND-ed long-term extension study. Presented at the American Society of Hematology (ASH) Annual Meeting 2025; December 6-9, 2025.

EFANESOCTOCOG ALFA
HEMOPHILIA A
FACTOR VIII REPLACEMENT THERAPY
Annualized Bleeding Rate

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