Weekly Efanesoctocog Alfa effective option for Preventing Bleeding among kids with Severe Hemophilia A: NEJM

Milan: An article published in The New England Journal of Medicine revealed that in children with severe hemophilia A, once-weekly prophylaxis with efanesoctocog alfa maintained high levels of factor VIII activity, typically above 40 IU per deciliter for at least 3 days and above 10 IU per deciliter for nearly 7 days after administration. This resulted in effective bleeding prevention. Efanesoctocog alfa was linked to primarily non-serious adverse events.

Weekly administration of efanesoctocog alfa maintains high, sustained factor VIII activity. It offers superior bleeding prevention compared to previous factor VIII prophylaxis in patients aged 12 and older with severe hemophilia A. However, there is limited data on the effectiveness of efanesoctocog alfa in children under 12 with severe hemophilia A.

Dr. Lynn Malec, M.D., Versiti Blood Research Institute, and the Division of Hematology and Oncology, Departments of Medicine and Pediatrics, Medical College of Wisconsin et. al. conducted a study on using efanesoctocog alfa prophylaxis for children with severe hemophilia A.

For this study, a phase 3, open-label trial was conducted involving previously treated patients under 12 years of age with severe hemophilia A. These patients received weekly prophylaxis with efanesoctocog alfa (50 IU per kilogram of body weight) over 52 weeks. The primary endpoint was the development of factor VIII inhibitors (neutralizing antibodies against factor VIII). Secondary endpoints included the annualized rates of treated bleeding episodes, effectiveness of bleeding treatment, safety, and pharmacokinetics.

The key findings of the research are as follows:

• A total of 74 male patients were enrolled, with 38 under the age of 6 and 36 between the ages of 6 and 12.
• No factor VIII inhibitors developed during the study.
• Most adverse events were nonserious, and no serious adverse events related to efanesoctocog alfa were reported by investigators.
• Among the 73 patients treated according to the protocol, the median annualized bleeding rate was 0.00 (IQR, 0.00 to 1.02), and the model-based mean annualized bleeding rate was 0.61 (95% CI, 0.42 to 0.90).
• 64% of patients had no treated bleeding episodes, 88% had no spontaneous bleeding episodes, and 82% had no joint bleeding episodes.
• 95% of bleeding episodes (41 out of 43) were resolved with a single injection of efanesoctocog alfa.
• Mean factor VIII activity at steady state was over 40 IU per deciliter for 3 days and over 10 IU per deciliter for nearly 7 days after dose administration.
• The geometric mean terminal half-life of efanesoctocog alfa was 40.0 hours.

Researchers have concluded that weekly administration of efanesoctocog alfa leads to high and sustained factor VIII activity, providing superior bleeding prevention compared to previous factor VIII prophylaxis in patients aged 12 and older with severe hemophilia A. However, there is limited data on the outcomes of efanesoctocog alfa treatment in children under 12 with severe hemophilia A.

Reference:

Malec L, Peyvandi F, Chan AKC, Königs C, Zulfikar B, Yuan H, Simpson M, Álvarez Román MT, Carcao M, Staber JM, Dunn AL, Chou SC, d'Oiron R, Albisetti M, Demissie M, Santagostino E, Yarramaneni A, Wong N, Abad-Franch L, Gunawardena S, Fijnvandraat K; XTEND-Kids Trial Group. Efanesoctocog Alfa Prophylaxis for Children with Severe Hemophilia A. N Engl J Med. 2024 Jul 18;391(3):235-246. doi: 10.1056/NEJMoa2312611. PMID: 39018533.