Efanesoctocog Alfa Prophylaxis Promising for Pediatric Severe Hemophilia A

Children with severe hemophilia A have benefits to gain from efanesoctocog alfa (Altuviiio; Sanofi/Campus) prophylaxis administered once a week, according to new research published in The New England Journal of Medicine.¹ The FDA approved efanesoctocog alfa, a high-sustained factor VIII replacement therapy, for the treatment of hemophilia A in 2023.² This medication was designed for either on-demand treatment or prophylaxis to help manage bleeding episodes in affected patients as well as for perioperative management.

Efanesoctocog alfa is a high-sustained factor VIII replacement therapy for the treatment of hemophilia A | image credit: Studios - stock.adobe.com

Previously in the XTEND-1 study (NCT04161495), the safety and tolerability of efanesoctocog alfa administered once-weekly was tested in patients with severe hemophilia A 12 years and older.¹ At a dose of 50 IU/kg, this treatment demonstrated superiority over prestudy factor VIII prophylaxis in terms of bleeding protection. Additionally, close to normal or normal activity for factor VIII was achieved throughout most of the week following treatment. At present, the authors reported on results from the XTEND-Kids (NCT04759131), which investigated the same dosage of efanesoctocog alfa for severe hemophilia A in previously treated patients younger than 12 years.

Included patients were previously treated with cryoprecipitate or recombinant or plasma-derived factor VIII for a minimum duration of 150 (aged ≥ 6 years) or 50 (aged < 6 years) exposure days. The researchers’ primary end point was the presence of neutralizing antibodies that counteract factor VIII (inhibitor development). Factors related to annual bleeding episode and treatment rates (location, type, treatment and management that was necessary, etc) constituted the secondary end points.

A total of 72 male patients completed this study (36 patients ≥ 6 years, 36 patients < 6 years). Most participants had prophylaxis with a factor VIII replacement therapy—with the exception of 1 who had on-demand treatment—prior to the start of the study.

The authors did not observe any inhibitor development throughout the cohort, nor did they witness antidrug antibodies. The adverse events (AEs) reported in association with efanesoctocog alfa were mainly nonserious. There were 62 patients (84%) who experienced at least 1 AE, of whom 3 patients (4%) were thought to have AEs related to their treatment. Nine patients (12%) reported more serious AEs; however, the authors noted these were not linked to their treatment. The common AEs reported by patients were severe acute respiratory syndrome coronavirus 2 test positivity, pyrexia, and upper respiratory tract infections. No thrombotic, embolic, anaphylaxis, or grade 3 or higher allergic reactions were noted. Furthermore, the AEs did not contribute to treatment discontinuation and no patients died during this study.

The average annualized bleeding rate was 0.61 (95% CI, 0.42-0.90). Overall, 47 patients (64%) did not have a treated bleeding episode, 65 (88%) were without spontaneous bleeding, and 61 (82%) did not experience any bleeding into their joints. In 95% (n = 41) bleeding episodes, a single injection of efanesoctocog alfa treated the incident. Additionally, treated patients were able to maintain coagulation factor levels in the near normal or normal range (> 40 IU/dL) for a period of 3 days following their prophylaxis; these levels were above 10 IU/dL for nearly a week post prophylaxis as well.

Children with severe hemophilia A typically endure taxing forms of treatment to manage their disease, the authors concluded; however, with little AEs arising from efanesoctocog alfa in this investigation, coupled with the lack of inhibitor development and the demonstrated promise this treatment holds for long-term joint health, this patient population could experience true benefits from the availability of this prophylaxis for their hemophilia A.

References

1. Malec L, Peyvandi F, Chan AKC, et al. Efanesoctocog alfa prophylaxis for children with severe hemophilia A. N Engl J Med. 2024;391(3):235-246. doi:10.1056/NEJMoa2312611

2. FDA approves once-weekly Altuviiio, a new class of factor VIII therapy for hemophilia A that offers significant bleed protection. News release. Sanofi. February 23, 2023. Accessed July 24, 2024. https://www.sanofi.com/en/media-room/press-releases/2023/2023-02-23-21-00-00-2614759