“In this study, once-weekly efanesoctocog alfa provided high sustained factor VIII activity and highly efficacious protection against bleeding episodes in children with severe hemophilia A, a population in which this goal has been difficult to achieve without burdensome treatment regimens,” report the authors in the study, published in The New England Journal of Medicine.
The results are from the phase 3, open-label XTEND-Kids study, in which first author Lynn Malec, MD, medical director of the Comprehensive Center for Bleeding Disorders and associate professor of medicine and pediatrics at The Medical College of Wisconsin, in Milwaukee, and colleagues enrolled 74 male pediatric patients with hemophilia A, including 38 under the age of 6 and 36 ages 6-12.
The participants received prophylaxis with once-weekly efanesoctocog alfa (50 IU per kg of body weight), for 52 weeks.
Prior to the treatment period, all patients had received factor VIII replacement therapy, with the exception of one who received the therapy on demand. Most (70%) received extended half-life products, such as doses twice a week or every 3 days, and the remaining 30% received standard half-life products, with dose regimens ranging from every 2 days to twice a week.
Over the course of the year-long study, none of the patients developed factor VIII inhibitors, neutralizing antibodies, a common complication in hemophilia A that prevents factor VIII replacement treatment from working to form clots.
In addition, no serious adverse events occurred that were determined to be related to efanesoctocog alfa.
“No inhibitors to factor VIII developed, most adverse events were not serious, and no adverse events led to discontinuation of efanesoctocog alfa,” the authors report.
In terms of efficacy, among 73 patients who were treated according to the protocol, the median annualized bleeding rate was 0.00 and the model-based mean rate was 0.61.
Overall, 47 patients (64%) experienced no treated bleeding episodes during the study, 65 (88%) had no spontaneous bleeding episodes, and 61 (82%) had no episodes of bleeding into joints.
Of 43 bleeding episodes, most (41; 95%) resolved with a single injection of efanesoctocog alfa.
Of note, “shortening the weekly administration interval was not deemed to be necessary in any patient during this study,” the authors add.
In comparison, other studies of children receiving other factor VIII products, including damoctocog alfa pegol, rurioctocog alfa pegol, and efmoroctocog alfa, show higher annualized bleeding rates of 2.9, 2.0, and 1.96, respectively, and studies showed the percentages of patients with no bleeding with those products were 23%, 38%, and 46%, respectively, compared with the 64% in the current study of efanesoctocog alfa.
“Although these clinical study results cannot be directly compared because of the differences in patient populations and study designs, the XTEND-Kids study showed favorable bleeding protection with efanesoctocog alfa prophylaxis as compared with these extended half-life factor VIII products,” the authors report.
Data on the once-weekly monoclonal antibody emicizumab, which has the important benefit of being administered subcutaneously instead of intravenously, is limited in children under age 12 with severe hemophilia A and without factor VIII inhibitors, the authors note.
However, the mean annualized bleeding rate with efanesoctocog alfa appears improved compared with that observed in a small Japanese study of 13 children who received emicizumab prophylaxis every 2 weeks or every 4 weeks, which showed annualized rates of treated bleeding episodes of 1.3 and 0.7 with the respective emicizumab regimens.