Efanesoctocog alfa, a first-in-class, bioengineered human factor VIII replacement therapy, shows safety and efficacy in the prevention of bleeding in children with severe hemophilia A, with benefits similar to those observed in adults, new research shows.
"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 aged 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.
Results Compare With Findings in Adults
The results are similar to those reported among adults in the previous XTEND-1 phase 3 study, which was the basis for US Food and Drug Administration (FDA) approval of the drug in 2023 for routine prevention and on-demand treatment for the control of bleeding episodes, in addition to perioperative surgery for adults.
That approval was extended to children as well at the time, based on earlier interim results from the XTEND-Kids trial.
The annualized bleeding rate among adult patients treated with efanesoctocog alfa decreased from 2.96 to 0.69 over the 52 weeks, which was a significantly greater improvement compared with prestudy prophylaxis with conventional factor VIII prophylaxis (P < .001).
In children and adults alike, the decreased bleeding events were accompanied by improvements in physical health, pain, and joint health.
"Weekly prophylaxis with efanesoctocog alfa has the potential to provide long-term preservation of joint health," the authors conclude.
Commenting in an editorial published concurrently with the study, Pratima Chowdary, MD, of the Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, England, underscored the need for a longer duration of prophylaxis, particularly in children.
"In children, the factor VIII protein has a shorter half-life than in adults, and intravenous administration of coagulation factors is particularly challenging, owing to poor venous access," she explains.
"In this context, a notable outcome in [the study] is the achievement of once-weekly prophylaxis in children with sustained factor VIII levels through the week, which augurs well for protection in the context of delayed or missed doses."
Dr Chowdary adds that limitations include that "the study participants had pre-existing tolerance of factor VIII because only those with previous exposure to factor VIII and without inhibitors were eligible for enrollment."
"As such, immunogenicity needs to be assessed in other patients, especially those with no previous treatment with factor VIII."
Further commenting to this news organization, Dr Chowdary emphasized "the key takeaway for patients with hemophilia is that the notion of a single, lifelong treatment is outdated."
"Regular reviews and adjustments to prophylaxis are necessary to ensure optimal control of hemophilia, aiming for zero bleeds each year," Dr Chowdary noted.
Furthermore, "the treatment regimen to achieve this must also align with the life goals of both patients and their parents," she said.
The study was supported by Sanofi and Sobi. The authors' and Dr Chowdary's disclosures are published with the study and editorial, respectively.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.