Hemlibra Effective at Controlling Bleeds in Acquired Hemophilia
Hemlibra is an antibody-based therapy that mimics factor VIII activity
One-month treatment with Hemlibra (emicizumab) and an immunosuppressive medication were effective for patients with acquired hemophilia at rapidly controlling bleeding and reducing the use of other therapies, a single-center study shows.
The researchers also noted that using less toxic immunosuppressive agents such as rituximab was effective at blocking the antibody production that’s a feature of this type of hemophilia.
The study, “Emicizumab for the treatment of acquired hemophilia A: retrospective review of a single-institution experience,” was published in Haemophilia.
Acquired hemophilia is an autoimmune disorder wherein the body’s immune system mistakenly sees factor VIII (FVIII), a blood clotting protein, as foreign and starts producing antibodies, called inhibitors, against it. As a result, FVIII activity diminishes, causing excessive and prolonged bleeding.
Treating this type of hemophilia is focused generally on controlling immediate bleeds and eliminating FVIII inhibitors, which is usually accomplished with immunosuppressive therapy (IST).
Hemlibra is an antibody-based therapy designed to bind to two specific targets simultaneously, mimicking the natural action of FVIII, and thereby preventing or lowering the frequency of bleeds. It’s approved for this indication in the U.S. in patients with hemophilia A, with and without inhibitors. Yet, only a few small studies involving Hemlibra with acquired hemophilia A have been carried out so far.
Hemlibra’s effect on acquired hemophilia assessed
Researchers from Boston, Massachusetts reviewed the experiences of 11 adults with acquired hemophilia who received off-label Hemlibra between January 2019 to December 2021. Off-label use means a therapy is treating a condition for which it hasn’t been officially approved.
Most said their bleeds were spontaneous, occurred in more than one site, and were classified as severe, with four patients requiring vascular embolization, a procedure that stops blood flow to a specific part of the body. Bleeds were classified as severe if they occurred in a limb, organ, or were life-threatening, with hemoglobin levels dropping to less than 8 g/dL, or reduced by at least 2 g/dL. Bleeds that required transfusion of at least two red blood cell units within 24 hours were also considered severe. Hemoglobin is the protein in red blood cells that carries oxygen.
Other treatments the patients might be taking — at any time following a bleed, while, before, or after starting Hemlibra — were also recorded.
Most patients were given Hemlibra in four weekly doses of 3 mg/kg, together with four weekly doses of 375 mg/m2 of rituximab, an IST that lowers the numbers of antibody-producing immune B-cells. Some were also taking recombinant FVIIa (rFVIIa), a bypassing agent, and the corticosteroid prednisone.
Hemlibra’s effectiveness at controlling bleeds was evaluated based on the dose and duration of other treatments and transfusions needed. The best response to IST was classified as partial remission (PR) or complete remission (CR). PR was defined as an improvement in FVIII activity levels by more than 50% and no bleeding events in the absence of bleed-control treatments for at least 24 hours. A CR is a PR plus a negative inhibitor test and IST discontinuation.
The activated partial thromboplastin time (aPTT) — a clot-based test that measures how long it takes for blood to clot — also was evaluated before patients started Hemlibra. Blood took a median of 81.2 seconds to clot (normal range, 30–40 seconds), results showed.
FVIII activity and levels of FVIII neutralizing antibodies also were measured before starting treatment. Patients had low FVIII activity (median of 1%) and were positive for FVIII inhibitors, which were found at a median titer level of 33 Bethesda Units per milliliter (BU/mL).
Improved clotting times
After starting Hemlibra, patients took a median of five days to show normal aPTT test results. The study also found that four weekly doses of 3 mg/kg Hemlibra may provide a rapid and sustained bleeding control, without having to maintain treatment for more than a month.
Patients required a median of two days of additional therapy or red blood cell transfusions after starting treatment with Hemlibra, underscoring its effectiveness, the results also showed.
“After initiating emicizumab, our patient cohort had minimal usage of other hemostatic therapies, which compares favorably to usage reported in international registries,” the researchers wrote.
None of the patients who didn’t undergo vascular embolization required rFVIIa or red blood cell transfusions more than eight days after starting Hemlibra.
“An emicizumab regimen that does not involve maintenance therapy would be advantageous and should be explored in a prospective study,” the researchers wrote.
Eight patients reached a CR, two achieved a PR, and one had refractory disease (failed treatment response). Best CR and PR responses were observed at a median of 163 days after starting rituximab with a median FVIII activity of 103%.
Based on these results, researchers emphasized that Hemlibra’s effectiveness at controlling bleeds “may provide a safe bridge to inhibitor eradication using lower-intensity ISTs that have reduced toxicity and treatment-related mortality (e.g. rituximab).”
The study also suggested “that IST of even lower intensity such as rituximab monotherapy may be effective,” they wrote.
No clotting events or infections were observed. Also, all but one patient achieved bleeding remission (bleeds did not come back) and inhibitors reappeared in two patients “suggesting late relapse is possible and that close monitoring remains important,” the researchers wrote, adding that larger prospective studies could confirm their findings.
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