While clinical trials will need to be done to fully assess Hemlibra as an AHA therapy, the researchers said this medication also has the potential to prevent bleeding, reduce the side effects of other treatments, and save costs.
The study, “Emicizumab for the treatment of acquired hemophilia A,” was published in the journal Blood.
In people with hemophilia A, the blood-clotting protein factor VIII (FVIII) is lacking or defective. The disease usually is congenital — meaning that it is present from birth and caused by mutations in the gene that codes for FVIII.
In AHA, however, there is no mutation. Instead, this disease type is characterized by the immune system producing antibodies (inhibitors) that block the function of the FVIII protein. Typical treatment for AHA involves the use of medications to prevent immediate bleeding, then using therapies that suppress the immune system to stop the production of the inhibitors.
Hemlibra contains an antibody that functionally mimics the activity of the FVIII protein. The therapy, which is administered by subcutaneous (under-the-skin) injection, is approved for the treatment of congenital hemophilia A, with or without inhibitors. Case reports have suggested it also may be useful for the treatment of AHA.
Now, researchers at the Medical University of Vienna, in Austria, reported on 12 individuals with AHA who were treated with Hemlibra at their institution. Six of the patients were male, and six were female; their median age was 74. Severe bleeding was observed in eight patients.
Hemlibra treatment was started a median of 8.5 days after initial bleeding. Other treatments, such as bypassing agents and replacement therapies, also were used in different combinations to control bleeding. All of the patients also were treated with immunosuppressive therapies.
They received a median of five doses of Hemlibra. The median initial dose was 2.7 mg/kg, with all dosages tailored based on individual patient characteristics.
Measurements of FVIII activity normalized within two days of starting Hemlibra treatment, but the assays used are oversensitive to Hemlibra and normalize even with tiny amounts of the therapy in the blood plasma, according to the researchers.
FVIII activity levels exceeded 5% of normal values after a median of four days. This increase “corresponded with clinically impressive cessation of bleeding,” the scientists wrote.
“No new or breakthrough bleeding events were observed after day 2,” they added. “Thus, even low emicizumab [Hemlibra] plasma concentrations seem to protect from bleeding in patients with AHA.”
Clinical remission, defined as FVIII activity higher than 50%, was achieved after a median of 105 days, about three and a half months. This was generally accompanied by reduced levels of FVIII inhibitors, consistent with the immune-suppressing therapy regimen used.
In terms of safety, the researchers reported two adverse events starting on Hemlibra. There was one instance of sepsis, which developed about two months into immunosuppressive treatment and 20 days after the last dose of Hemlibra. Additionally, an instance of stroke occurred nearly two weeks into treatment in a 79-year-old woman who had a history of inflammation, repeated surgeries with general anesthesia, and high body fat — all considered risk factors for blood clots.
Importantly, the researchers found that Hemlibra had “the potential to prevent bleeding, reduce side effects of immunosuppressive therapy, save costs, and protect patients from [clot-related] complications.”
“Administration of emicizumab seems to be an important new concept for hemostatic [bleeding control] therapy of patients with AHA,” they concluded.
Clinical trials will be needed in people with AHA to fully discern the value of Hemlibra as a potential treatment, the team noted.