3 years on Hemlibra keeps joints healthy in kids with hemophilia A
Analysis covers follow-up data on 30 boys in Japan trial
Hemlibra (emicizumab-kxwh) safely supports joint health in children with hemophilia A without inhibitors through three years of treatment, according to interim data from a post-marketing study in Japan.
The ongoing study, AOZORA (jRCT1080224629), is evaluating the long-term safety of Hemlibra and its impact on joint health in children ages 11 or younger.
“[Hemlibra] is well tolerated and appears to maintain or improve joint health in pediatric [people with hemophilia A],” the researchers wrote.
The results were detailed in the study, “AOZORA study: Three-year interim analysis of safety and joint health in pediatric people with hemophilia A receiving emicizumab prophylaxis,” published in Research and Practice in Thrombosis and Haemostasis. The AOZORA trial is sponsored by Chugai Pharmaceutical, which markets the therapy along with Genentech. Several of the study’s authors are employees or consultants of Chugai.
Hemophilia A is caused by a deficiency in factor VIII (FVIII), a protein the body needs for blood clotting, which leads to excessive and prolonged bleeding, often inside the joints. Joint bleeds frequently begin as soon as a child starts crawling and walking, usually in the ankles, knees, and elbows. Repeated bleeds can lead to pain, stiffness, and lasting joint damage.
Antibody therapy given by injection
Preventive treatment (prophylaxis) has traditionally relied on factor replacement therapies, or regular FVIII infusions into the bloodstream. However, joint bleeds can still occur, and some children develop inhibitors, antibodies that block FVIII and reduce the treatment’s effectiveness.
Hemlibra is an antibody-based therapy designed to prevent or reduce bleeding in children and adults with hemophilia A, regardless of whether they have FVIII inhibitors. Given as an under-the-skin injection, it works by linking two other clotting factors, factor IX (FIX) and factor X (FX), to mimic the role of FVIII and help the blood clot properly.
While the therapy has shown lasting safety and efficacy in reducing bleeds, “there is a lack of long-term data on joint health in children receiving [Hemlibra] prophylaxis through to adulthood,” the researchers wrote.
They analyzed three-year follow-up data from 30 boys enrolled in the AOZORA study.
Twenty patients were starting Hemlibra for the first time, while 10 had continued treatment after the earlier Phase 3 HOHOEMI trial in Japan, which evaluated the therapy’s safety and efficacy in 13 children aged 11 or younger. Hemlibra was administered as a routine part of their care once a week, every other week, or every four weeks.
The study involved infants younger than a year to 11-year-old boys, with a median age of 4.2 at the study’s start.
Nearly all (90%) had been receiving factor replacement therapies, with most starting before age 2 and continuing for more than a year.
Over the three years of follow-up, five of the 30 boys (16.7%) experienced side effects thought to be related to Hemlibra, including six injection-site reactions and one case of low red blood cells. Seven serious medical events occurred in five boys, but none was linked to the therapy. No blood-clotting complications were reported, and no child required stopping or adjusting a dose due to side effects.
The researchers monitored joint health using physical exams and MRI scans of the ankles and knees. Scans were available for 29 boys at the study’s start and 26 boys after three years. At follow-up, 11 boys (42.3%) had no visible signs of joint changes on either scan. The remaining 15 boys, who had MRI changes at the beginning of the study, showed different patterns over time: Scans improved in nine, remained unchanged in two, and worsened in four.
Initially, seven boys exhibited early signs of joint damage, including thickening of the joint lining (synovial hypertrophy) or iron accumulation in the joint (hemosiderin deposition). These findings improved in all affected joints, with most fully disappearing by the three-year mark. Two children had deeper bone-related changes, but these either improved or did not worsen during follow-up.
Physical examinations also showed stable joint function overall. Of 27 boys assessed at three years, 18 (66.7%) continued to show no joint issues, five improved, three showed new or increased signs of problems, and one showed no change from the study’s start.
Treated bleeds of any kind fell from 3.6 per year to 0.8 per year with Hemlibra, including a drop in spontaneous bleeds from 1.3 per year to 0.2 per year and treated joint bleeds from 0.5 per year to 0.2 per year.
“This 3-year interim analysis of the AOZORA study confirms the safety profile of [Hemlibra], and, for the first time, demonstrates the efficacy of [Hemlibra] prophylaxis in maintaining joint health and reversing synovial hypertrophy and hemosiderin deposition in pediatric [Hemophilia A],” the researchers wrote.
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