Real-world study backs safety of Hemlibra for acquired hemophilia A
Japan is the only country where the treatment has approval for this indication
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- A real-world study has confirmed Hemlibra's safety for acquired hemophilia A when combined with immunosuppressants.
- AHA involves FVIII inhibitors causing bleeding; Hemlibra mimics FVIII, reducing bleeds.
- Treatment increased FVIII activity and decreased inhibitors, with few treatment-related adverse events.
Hemlibra (emicizumab) alongside immunosuppressive therapy appears safe for use in acquired hemophilia A (AHA), according to initial results of a real-world study in Japan, the only country where Hemlibra has approval for this indication.
“At this interim analysis, there were no unexpected safety concerns for … patients with AHA treated with [Hemlibra], and the consistently low incidence of bleeding supports the potential role of [Hemlibra] in effectively preventing AHA-related bleeds,” researchers wrote.
In the U.S., the European Union, and other regions, Hemlibra is approved for the treatment of inherited hemophilia A, but not AHA.
The study, “Real-World Use of Emicizumab in Patients With Acquired Haemophilia A: An Interim Safety Analysis of a Large-Scale Post‑Marketing Surveillance Study,” was published in Haemophilia. Hemlibra’s developer, Chugai Pharmaceutical, now part of the Roche group, sponsored the study.
Hemlibra mimics activity of clot-forming protein
In AHA, the immune system develops factor VIII (FVIII) inhibitors, antibodies that target the clot-forming protein FVIII and reduce its activity. The result is easy and prolonged bleeding. These symptoms are similar to those seen in inherited, or congenital, forms of hemophilia, however, the causes and therapeutic strategies differ.
Treatment for AHA often relies on immunosuppressants, which decrease self-directed immune attacks. Such bypassing agents as recombinant FVIIa (rFVIIa) therapies, which boost clotting activity while bypassing the need for FVIII, can also help control and prevent bleeding. Other options for AHA remain limited.
Hemlibra may provide an alternative treatment for some people with AHA. It binds to certain clotting proteins, mimicking FVIII activity, and has wide approval for bleed prevention in hemophilia A.
“Despite reports of [Hemlibra] use for AHA, the regimens used were inconsistent and not necessarily tailored to the disease pathology,” the researchers wrote.
To more formally assess this use, Chugai sponsored a Phase 3 trial in Japan. Results demonstrated that the medication could also be effective in AHA. Japanese regulators approved Hemlibra for AHA in 2022, providing an opportunity to assess long-term safety in a larger patient population.
Now, researchers have conducted a post-marketing study “to collect information on the use and safety of [Hemlibra] in patients with AHA in real-world clinical practice in Japan.”
Most safety-related events not considered treatment-related
The study enrolled 167 participants, 51 of whom completed treatment with Hemlibra for this planned interim analysis. Two-thirds were men, with a median age of 76. Investigators estimated that this accounted for 40% of all AHA patients in Japan who received Hemlibra treatment during this period.
Participants received a single subcutaneous (under-the-skin) Hemlibra dose of 6 mg/kg, followed by a 3 mg/kg dose the next day. After this, they received weekly 1.5 mg/kg doses until their FVIII activity had increased past a prespecified cutoff, or they discontinued treatment due to side effects, death, or hospital transfer. Alongside Hemlibra, they received immunosuppressants as needed.
Of the 51 participants, 37 completed a course of Hemlibra, 13 discontinued the therapy, and one was still taking Hemlibra.
About half of the participants experienced safety-related events during the study, but most weren’t considered treatment-related. Investigators believe that two serious events — a severe urinary tract infection and a case of hemorrhoids — may have been directly related to Hemlibra. There were nine deaths during the study, none of which were related to Hemlibra.
Based on these safety findings, “the benefit–risk profile of [Hemlibra] remains favourable,” the researchers wrote.
This study demonstrates that these measures provide a reliable framework for [Hemlibra] use for AHA in clinical practice.
Participants who completed treatment had a median starting FVIII activity of 1 IU/dL. This increased to 59.1 IU/dL after completing Hemlibra, within the expected range for healthy individuals. Activity continued to increase in the following weeks. FVIII inhibitor levels also decreased during treatment, suggesting lower autoimmune activity.
“Although a comparison with a non-[immunosuppressive therapy] group was not possible in this observational study, findings suggest that the combination of [Hemlibra and immunosuppression] may enable recovery of FVIII levels in many patients,” the team noted.
Measuring the frequency of bleeding episodes that required treatment with rFVIIa allowed the team to estimate efficacy. They found that most treated bleeds occurred during the first week of Hemlibra treatment. This “suggests that AHA-related bleeding had not completely stopped prior to initiating [Hemlibra],” the researchers wrote. However, there was no control group to compare this to.
These results support safety measures such as regular FVIII activity and FVIII inhibitor testing throughout real-world Hemlibra use in AHA, according to the team.
“This study demonstrates that these measures provide a reliable framework for [Hemlibra] use for AHA in clinical practice,” they wrote.
As the study continues, the investigators hope to better understand how clinicians in Japan use Hemlibra to treat AHA.
“The final analysis will provide further details on long-term treatment and outcomes for AHA patients receiving [Hemlibra],” the researchers wrote.
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