Prophylactic (preventive) treatment with Hemlibra (emicizumab) safely and effectively lowers bleeding rates in children and adolescents with severe hemophilia A, according to a real-life study from Israel.
The therapy’s effectiveness was independent of the presence of inhibitors (antibodies) against synthetic formulations of factor VIII (FVIII) — the missing clotting factor in people with hemophilia A.
These findings, along with results from the previous HAVEN 1 (NCT02622321), HOHOEMI (JapicCTI‐173710), and HAVEN 2 (NCT02795767) Phase 3 trials, support Hemlibra’s use in the hemophilia A pediatric population, regardless of inhibitor status.
Data also suggested that routine laboratory monitoring may be unnecessary in most asymptomatic young patients, but warranted in those with bleedings, as they may have developed antibodies against Hemlibra, researchers said.
The study, “Emicizumab treatment and monitoring in a paediatric cohort: real‐world data,” was published in the British Journal of Haematology.
Hemlibra, administered as an under-the-skin injection, is a bypassing agent that mimics FVIII activity, helping blood to clot normally. Initially developed by Japan-based Chugai Pharmaceutical, Hemlibra is now being co-developed and marketed by Genentech, a Roche subsidiary.
The therapy is currently approved in more than 90 countries as a routine preventive treatment for hemophilia A patients with FVIII inhibitors. It also is approved globally, including in the U.S., Europe, and Japan, as a prophylactic treatment for those without inhibitors.
While Hemlibra’s safety and effectiveness was evaluated in both children and adults with hemophilia A in clinical trials, real-world data on Hemlibra’s use and monitoring in pediatric patients remain limited.
Researchers at the Israeli National Hemophilia Center set out to evaluate the safety, effectiveness, and laboratory monitoring of Hemlibra prophylaxis in children with severe hemophilia A, regardless of inhibitor status.
They prospectively analyzed data on 40 children followed at their center, with a median age of 5.5 years (range: 1 month to 18.5 years). Nine were less than 1 year old.
A total of 18 children were positive for FVIII inhibitors, while 22 were not. The proportion of inhibitor-positive patients was higher among infants (89%) than older children (32%).
Hemlibra’s loading dose (3 mg/kg) was given once a week for four weeks, followed by weekly maintenance doses (1.5 mg/kg). Bleedings, traumas, adverse events, and surgeries were documented during a median follow‐up of 45 weeks, or about 10 months (range: eight to 102 weeks).
Treatment monitoring was based on routine laboratory tests before and during treatment. These included measures of blood levels of Hemlibra, overall blood clot formation — assessed through the activated partial thromboplastin time (aPTT) test — and effectiveness at inducing blood coagulation, as assessed with the thrombin-generation assay.
Results showed that 20 patients (50%) had trauma-related bleedings during the study period, with no reports of spontaneous bleedings. Most bleeding episodes were treated with a single dose of FVIII or NovoSeven (factor VIIa), by Novo Nordisk.
Such a high proportion of children experiencing bleedings may be associated with the study’s long follow-up period, the researchers said. Children’s median annualized bleeding rate fell after Hemlibra initiation, with no differences between those with or without inhibitors.
Treatment duration was significantly longer in children with FVIII inhibitors, and the risk of having a bleeding event was significantly associated with the treatment’s length.
A total of 12 children underwent 16 minor surgical procedures, with no blood clot-related complications or thrombotic microangiopathy (damage of the smallest blood vessels due to blood clots), consistent with data from previous reports.
Hemlibra was generally safe and well tolerated, with no serious treatment-related adverse events. The most commonly reported side effect was an injection site reaction (10%), which were mostly mild and did not result in treatment discontinuation.
Hemlibra’s blood levels increased after treatment initiation, which was associated with normalized blood clotting speed and an increase (but not normalization) in the effectiveness of blood clotting.
Blood clotting did not differ between children experiencing bleedings and those who did not. But it was lesser in the younger group, consistent with a previously reported age-dependent increase in such effectiveness.
“As all bleedings were trauma‐related, laboratory monitoring could not predict bleeding risk,” the researchers wrote, adding that “routine monitoring of most asymptomatic patients may be redundant.”
However, laboratory monitoring is particularly needed in children with bleedings while on Hemlibra, as antibodies against the therapy have been previously reported, they added.
Measuring Hemlibra blood levels or blood clotting speed are practical and accessible tests in the clinical setting, the scientists said. Future studies are needed to better assess the clinical implications of routine laboratory monitoring, particularly in patients undergoing surgery.
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