Efanesoctocog Alfa Improves Bleeding Regardless of Age in Hemophilia A, With Lynn Malec, MD, MSc

Once-weekly efanesoctocog alfa is both well tolerated and efficacious in providing bleed protection to adult, adolescent, and child patients with severe hemophilia A, according to results from the XTEND-ed study.1

These data were presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition by Lynn Malec, MD, MSc, an associate professor in the division of hematology and oncology at the Medical College of Wisconsin.1

Efanesoctocog alfa is a first-in-class high-sustained factor VIII (FVIII) replacement therapy that decouples recombinant FVIII from endogenous von Willebrand factor. The prior phase 3 XTEND-1 and XTEND-Kids studies saw once-weekly efanesoctocog alfa exhibit effective bleed protection and provide FVIII activity within the normal to near-normal (>40%) range for 4 and 3 days, respectively, at steady state.1,2

“I think the exciting data, besides just the aspects of the inhibitors, is how well patients are protected from bleeding,” Malec told HCPLive in an exclusive interview. “We typically measure that by way of annualized bleed rates in patients, and what we saw in the study was that patients across the age span continue to have really great bleed protection while on the extension study.”

Participants who completed the XTEND-1 or XTEND-Kids study could continue once-weekly 50 IU/kg of efanesoctocog alfa prophylaxis in XTEND-ed, an ongoing multicenter, open-label, long-term study. The primary endpoint for this trial was incidence of FVIII inhibitor development, while secondary endpoints included annualized bleed rates (ABRs), efficacy for bleed treatment, and safety.1

Ultimately, 146 adult and adolescent patients rolled over from the XTEND-1 to XTEND-ed baseline. The median age was 37 years (range, 13-74), and the median treatment duration in XTEND-ed was 166 weeks (range, 14.1-192.7), which comprised a median of 167 days (range, 14-200) exposure days (EDs).1

During the trial, the mean ABR for day 1-month 12 (n = 146) was 0.7 (standard deviation [SD], 1.31), months 12-24 (n = 141) was 0.62 (1.23), and months 24-36 (n = 132) was 0.45 (1.24), with 96/146 (65.8%), 96/141 (68.1%), and 103/132 (78%) of participants with zero bleeds, respectively. The mean model-based ABR for the efficacy period was 0.6 (95% CI, 0.47-0.76) for overall treated bleeds, and 0.2 (95% CI, 0.15-0.28) and 0.29 (95% CI, 0.22-0.39) for spontaneous and traumatic bleeds, respectively. Additionally, of 252 treated bleeding episodes, 94% were resolved with 1 efanesoctocog alfa injection.1

Among children, 71 patients rolled over from XTEND-kids to XTEND-ed; median treatment duration was 116.7 (range, 36.3-152.6) weeks, comprising a median of 116 (range, 11-153) EDs. The mean ABR evaluated for day 1-month 12 (n = 71) was 0.68 (SD, 1.13) and months 12-25 (n = 62) was 0.49 (0.82), with 46/71 (64.8%) and 41/62 (66.1%) of participants with zero bleeds, respectively. The mean model-based ABR was 0.64 (95% CI, 0.48-0.85) for overall treated bleeds, and 0.08 (95% CI, 0.04-0.15) and 0.44 (95% CI, 0.31-0.62) for spontaneous and traumatic bleeds, respectively. Of 89 episodes, 91% (81) were resolved with 1 efanesoctocog injection. No FVIII inhibitors were noted in either the adult/adolescent or child groups at any point during the study.1

“I treat patients across the age spectrum – both pediatric and adult patients – and I think the aspect of zero bleeds really is the new benchmark,” Malec told HCPLive. “Are you on a therapy to be bleed-free or to have zero bleeds? I think that data is, in my mind, the gold standard.”

Editor's Note: Malec reports disclosures with Biomarin, Genentech, Novo Nordisk, Sanofi, Shire, and Takeda, among others.

References

1. Susen S, Chan A, Chowdary P, 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. Abstract presented at the 67th American Society of Hematology Annual Meeting. Orlando, Fl. December 6-9, 2025.

2. Bioverativ. A phase 3 open-label interventional study of intravenous recombinant coagulation factor VIII fc-von Willebrand factor-XTEN fusion protein, efanesoctocog alfa (BIVV001) in patients with severe hemophilia A (XTEND-1). ClinicalTrials.gov Identifier: NCT04161495. Updated September 17, 2025. Accessed December 16, 2025. https://clinicaltrials.gov/study/NCT04161495