Long-Term Data Demonstrate Emicizumab Safety, Efficacy in Hemophilia A

New long-term data tracking the safety and efficacy of emicizumab (Hemlibra; Genentech) prophylaxis in patients with hemophilia A without factor VIII (FVIII) inhibitors show the therapy continues to be effective several years after initiation.

No new safety signals were identified in the analysis, which followed patients who had participated in the HAVEN 3 and 4 trials. The report was published in Research and Practice in Thrombosis and Hemostasis.

Historically, people with hemophilia A have been treated with prophylactic factor replacement therapy, explained the study authors. The therapy was delivered intravenously and required multiple treatments per week to manage the risk of bleeding and associated joint damage.

Emicizumab is not a factor therapy; it is a bispecific monoclonal antibody that bridges activated factors IX and X to mimic the function of missing or deficient FVIII, the authors said. Unlike factor replacement therapy, emicizumab can be administered subcutaneously, and doses are only required every 1 to 4 weeks, depending on the dosage.

Emicizumab is a bispecific monoclonal antibody that bridges activated factors IX and X to mimic the function of missing or deficient FVIII | Image Credit: shidlovski - stock.adobe.com

The HAVEN 3 and 4 studies looked at the safety and efficacy of the therapy in people with hemophilia A. HAVEN 3 included patients without FVIII inhibitors, and participants were given maintenance doses of 1.5 mg/kg weekly or 3.0 mg/kg every other week. HAVEN 4 included patients with and without FVIII inhibitors; participants were given 6-mg/kg doses every 4 weeks.

The authors said their new analysis of long-term outcomes in people with hemophilia A without FVIII inhibitors is important because thus far information about this patient group has been limited.

These new data tracked 191 participants to a median duration of emicizumab exposure of 248.1 weeks across both studies. Most of the participants (79%) were from HAVEN 3; the rest were enrolled in HAVEN 4. Over the first 24 weeks of treatment, the investigators found that the mean annualized bleed rate (ABR) for treated bleeds was 2.0 (95% CI, 0.23-7.15). By weeks 217 to 240, the ABR for treated bleeds was 0.9 (95% CI, 0.01-5.28).

Ninth-eight percent of participants experienced at least 1 adverse event (AE). Just over one-third of participants (37.2%) experienced a treatment-related AE, and 185 treatment-related AEs were reported overall. The most common treatment-related AE was injection-site reactions, which were experienced by 28.8% of patients. Between 2 and 5 patients reported each of the following treatment-related AEs: headaches, rash, pruritus, and nausea. Twenty-three percent of participants had a serious AE, although none of those were judged to be treatment related. Two cases of thromboembolic events were deemed unrelated to the therapy.

The investigators said the long-term data are encouraging.

“The overall ABRs in both studies remained consistently low throughout long-term follow-up, with no unexpected or new safety signals observed,” they said. They also said one limitation of the study is that bleed data were based on self-reports and therefore could be incomplete or subjective. Still, they noted that patient compliance with their reporting questionnaire remained above 90% despite the long duration of the reporting period.

The study investigators added said the low bleed rates allowed more than 95% of target joints present at the studies’ baselines to resolve within the first year of emicizumab therapy.

“This indicates that emicizumab prophylaxis, given over longer periods of time, may be able to maintain or improve joint health, potentially having a notable impact on quality of life,” they wrote.

They added that a high proportion of patients in both studies chose to continue using emicizumab after the trial, either through a posttrial access program or by switching to commercial emicizumab.

Overall, the authors said these data suggest the therapy is a meaningful long-term therapeutic strategy for this patient group.

“With nearly 5 years of follow-up and 729.3 participant-years of exposure, these data build on previous findings of a favorable long-term benefit-risk profile for emicizumab prophylaxis in people with hemophilia A without inhibitors, with consistent bleed prevention and no new or unexpected safety signals,” they concluded.

Reference:

Mahlangu J, Jiménez-Yuste V, Ventriglia G, et al. Long-term outcomes with emicizumab in hemophilia A without inhibitors: results from the HAVEN 3 and 4 studies. Res Pract Thromb Haemost. 2024;8(2):102364. doi:10.1016/j.rpth.2024.102364