Emicizumab prophylaxis in children with hemophilia A with factor VIII inhibitors in China (HAVEN 5)

To the Editor: Hemophilia A (HA) is a congenital bleeding disorder associated with spontaneous or traumatic bleeds, primarily affecting males. 1 HA is characterized by a deficiency or lack of coagulation factor VIII (FVIII), causing recurrent bleeding, predominantly into joints, muscles, and soft tissues. 1 In children with HA, especially infants, early bleed control is crucial to prevent potentially life-threatening bleeding and the development of joint arthropathy over time. 2 Emicizumab is a recombinant, humanized, bispecific monoclonal antibody that bridges activated factor IX (FIX) and factor X (FX) to substitute for the function of deficient activated FVIII, thereby improving hemostasis in people with HA (PwHA). The long half-life of emicizumab allows for once-weekly (QW), every 2 weeks (Q2W), and every 4 weeks (Q4W) dosing regimens. 3 Emicizumab was approved in China in 2018 for adults and children with HA and inhibitory antibodies to FVIII (inhibitors), and in 2021 for adults and children with severe HA without inhibitors; however, data in the Chinese pediatric population with HA remain limited. The Phase 3 HAVEN 5 study (NCT03315455, https: //clinicaltrials. gov/study/NCT03315455? term=NCT03315455%20 the protocol was approved by the Institutional Review Boards/Independent Ethics Committees at each participating site and carried out in accordance with applicable regulations. Adult/adolescent participants (aged ≥12 years with severe HA without FVIII inhibitors, or HA of any severity with FVIII inhibitors) were randomized to one of three arms (arms A, B, or C), 4 comparing emicizumab prophylaxis with no prophylaxis. Pediatric participants (30 μg/mL) thereafter. Laboratory tests for pharmacodynamic and safety biomarkers showed results consistent with previous studies. 10 Following the first emicizumab dose, aPTT shortened and remained within or below the reference range throughout the study. This shortening should not be considered indicative of normalization of hemostasis, as aPTT was shortened to within the normal range during the loading period, when emicizumab concentrations had not yet reached therapeutic levels. FVIII-like activity increased during loading and was maintained. No effect was seen on D-dimer and prothrombin time from emicizumab treatment, and levels remained stable throughout the study. A limitation of this study is the small population size (15 participants) ; for this reason, results should be interpreted with caution. Furthermore, the bleed and medication questionnaire that was used to report bleeds was completed by caregivers and was reliant on descriptions of symptoms from the child, which could have resulted in over- or under-estimation of bleeds. In conclusion, prophylaxis with emicizumab was well tolerated in Chinese children (aged <12 years) with HA and high-titer FVIII inhibitors, and safety findings were consistent with the known safety information available for emicizumab treatment. Emicizumab demonstrated substantial and clinically meaningful bleed control, similar to that observed in the adult/adolescent population of HAVEN 5 and in other Phase 3 studies. Acknowledgment The HAVEN 5 study was sponsored by F. Hoffmann-La Roche Ltd. The authors thank the study participants and their families, as well as the study investigators, research coordinators, and nurses. Third-party medical editing assistance, under the direction of the authors, was provided by Katie Smith, PhD, and Naziyat Khan, PhD, of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd. Data sharing statement For up-to-date details on Roche’s global policy on sharing clinical information and how to request access to related clinical study documents, see https: //go. roche. com/dataₛharing. Anonymized records for individual patients across more than one data source external to Roche cannot, and should not, be linked because of the potential increase in risk of patient reidentification. Conflicts of interest RW declares no conflict of interest. JS declares no conflict of interest. QH declares no conflict of interest. CS is an employee and stockholder of F. Hoffmann-La Roche Ltd, and co-inventor of a patent related to an anti-FIXa/FX bispecific antibody. AK is an employee and stockholder of F. Hoffmann-La Roche Ltd. DL is an employee of Roche (China) Holding Ltd. YX is an employee of Roche (China) Holding Ltd. YZ is an employee of Roche (China) Holding Ltd. RY declares no conflict of interest.