Study: Hemlibra Is Safe, Effective in Young Hemophilia A Patients Without Inhibitors

Hemlibra (emicizumab) is safe and effective to treat children younger than 12 who have hemophilia type A and are negative for antibodies against synthetic factor VIII, results from a Japanese clinical study show.

The trial findings were reported in the study, “A multicentre, open‐label study of emicizumab given every 2 or 4 weeks in children with severe haemophilia A without inhibitors,” published in the journal Haemophilia.

Hemophilia A is characterized by a deficiency of a protein necessary for blood clotting, known as factor VIII (FVIII). Standard of care for these patients is based on replacement of the lacking protein by intravenous administration of synthetic formulations of FVIII.

Despite the efficacy demonstrated by this therapeutic approach, approximately 30% of patients with severe hemophilia A receiving replacement therapy develop antibodies against FVIII (also known as FVIII inhibitors). Presence of these inhibitors in the blood renders FVIII products ineffective and leads to impaired blood clotting.

Hemlibra is an engineered antibody initially developed by Chugai Pharmaceutical to mimic the activity of a blood clotting cofactor, thus bypassing the need for FVIII. The antibody is being further developed and commercialized by Genentech.

Clinical effectiveness of Hemlibra for bleeding prevention has been demonstrated in adults and adolescents with or without inhibitors through the HAVEN 1 (NCT02622321), HAVEN 3 (NCT02847637), and HAVEN 4 (NCT03020160) trials; and in pediatric patients with inhibitors in the HAVEN 2 (NCT02795767) trial.

To date, no clinical study addressed the safety and effectiveness of Hemlibra in pediatric patients without inhibitors. To overcome this knowledge gap, Japanese researchers conducted the HOHOEMI study (JapicCTI‐173710).

The study enrolled 13 children ages 4 months to 10 years with confirmed hemophilia A without FVIII inhibitors. They were randomly assigned to receive subcutaneous (under the skin) injections of Hemlibra in dosages of 3 mg/kg every two weeks or 6 mg/kg every four weeks for at least 24 weeks (almost six months).

Seven children, including five from the four-weeks dosing regimen, did not experience any bleeding event during the study. The remaining patients experienced nine bleeding events that were successfully managed by episodic treatment with FVIII replacement therapy.

Assessment of the annualized bleeding rates (ABR), according to the number of bleeding events reported during the study, was found to be 1.3 and 0.7 with Hemlibra injection every two or four weeks. These ABR results were similar to those reported in previous HAVEN trials in adults and adolescents with hemophilia A.

When asked which treatment was preferable, all caregivers said they would select Hemlibra over their child’s previous FVIII replacement treatment.

The levels of Hemlibra remained stable throughout the study in both treated groups. No cases of recurrent or new development of FVIII inhibitors were described.

In general, the treatment was shown to be safe, with most adverse events reported being unrelated to the treatment itself but to traumatic injuries, such as nosebleeds and falls. Only one treatment-related adverse event — an injection site reaction — was reported.

Taken together, the results showed Hemlibra’s “remarkable efficacy and favorable safety … in children with severe hemophilia A without inhibitors,” researchers stated. “[Hemlibra] exposure observed in this study was within the variability observed in the preceding adult/adolescent studies.”

They concluded, “These results confirm the appropriateness of applying the [twice weekly and once monthly] regimens” of Hemlibra in this young hemophilia A population.