Hemlibra Found Effective for Severe Hemophilia A in Clinical Setting

Preventive, or prophylactic, treatment with Hemlibra (emicizumab) safely and effectively managed bleeding in adults and children with severe hemophilia A, a real-world study has found.

The study, “Emicizumab prophylaxis: Prospective longitudinal real‐world follow‐up and monitoring,” was published in the journal Haemophilia.

Originally developed by Roche’s subsidiary Chugai Pharmaceutical and now marketed by Genentech, Hemlibra is a bispecific antibody — a protein that is able to bind to two targets at the same time — that is designed to mimic the function of factor VIII (FVIII), the clotting protein that is missing or defective in hemophilia A patients.

Previous clinical trials have demonstrated that when given as a preventive measure, Hemlibra safely and effectively lowered the number of bleeds in patients with severe hemophilia A, including those with and without FVIII inhibitors — neutralizing antibodies that render replacement therapies less effective.

However, “real-world data on patients’ laboratory monitoring are scarce,” the researchers wrote.

To evaluate the safety and efficacy of Hemlibra in a real-world setting and to understand how laboratory tests can help monitor the disease and response to treatment over time, researchers followed a group of patients with severe hemophilia A, with and without FVIII inhibitors, who received prophylactic treatment with Hemlibra.

The study included 107 patients, 58 of whom were children with a median average age of 6 years. All were Caucasian and started receiving prophylactic treatment at a median age of 14 for a median of 67 weeks (up to 144 weeks).

Of the 107 patients included in the analyses, 31 (29%) had FVIII inhibitors. Patients with FVIII inhibitors were treated for nearly double the time of those without inhibitors (median of 96 vs. 53 weeks).

Hemlibra prophylaxis decreased the annual bleeding rate (ABR) — the total number of bleeds patients experience in a year — with 53 patients experiencing no bleeds. Patients who had bleeding episodes were treated for about 50% longer than those with an ABR of zero (median 82 vs. 53 weeks).

Most bleeds (94%) in children were trauma-related, whereas most bleeds (61%) in adults were spontaneous joint bleeds. The chance of experiencing trauma-related bleeds was linked to longer follow-up duration.

Four patients experienced major bleeds, with a fatal outcome in one infant, who also presented with central venous line thrombosis (a common complication of catheter insertion). No other serious adverse events were noted.

Seven patients (six adults and one adolescent) decided to stop treatment after a median of 31 weeks for various reasons, including severe headaches. Headaches stopped once Hemlibra was discontinued.

Laboratory tests showed the plasma levels of Hemlibra increased significantly between week two and five after treatment initiation. They remained high thereafter in all but one patient, who was suspected of having developed antibodies against the medication.

Thrombin generation (TG) — a measure of blood coagulation — was increased and sustained over time. However, it could not predict the risk of bleeding. Therefore, “routine TG monitoring is not obligatory,” the researchers wrote, adding that “further studies are warranted in selected patient populations.”

Hemlibra prophylaxis also reduced the levels of FVIII inhibitors by more than fourfold in patients who had developed them.

In a large group of adults and children with severe hemophilia A, Hemlibra prophylaxis “was mostly safe and well tolerated, although 50% of patients experienced breakthrough bleeds,” the researchers concluded.

Of note, three of the researchers have received honoraria from Roche.