In a recent study published in Research and Practice in Thrombosis and Haemostasis, researchers reported on the long-term efficacy and safety of emicizumab prophylaxis in individuals with hemophilia A (HA) without FVIII inhibitors in the HAVEN 3 and HAVEN 4 studies.
HAVEN 3 and HAVEN 4 are open-label, phase III studies.
The authors wrote, “Previous studies evaluating the long-term safety and efficacy of emicizumab prophylaxis have been conducted; however, data on the long-term outcomes of emicizumab prophylaxis specifically in individuals without FVIII inhibitors are limited. Here, we describe the data on people with HA without FVIII inhibitors from the long-term follow-up of the HAVEN 3 and 4 studies.”
The researchers indicated that participants received emicizumab maintenance doses of 1.5 mg/kg every week, 3 mg/kg every 2 weeks (HAVEN 3), or 6 mg/kg every 4 weeks (HAVEN 4), and researchers evaluated long-term efficacy and safety.
The studies included 191 patients, with 151 and 40 individuals without FVIII inhibitors who received emicizumab in HAVEN 3 and 4, respectively.
The results revealed that the average (95% CI) annualized bleed rate for treated bleeds was 2.0 (0.23-7.15) for Weeks 1 to 24, declining to 0.9 (0.01-5.28) by Weeks 217 to 240. When evaluated over 24-week periods, the percentage of participants with no treated bleeds augmented from 62.2% to 78.8% in the same period.
Additionally, 48.8% of the participants had no spontaneous or traumatic joint bleeds over the efficacy period. Of the 306 target joints present before the initiation of treatment, 291 (95.1%) did not have spontaneous or traumatic bleeds in the first year after therapy was initiated. During the last 52 weeks, 297 (97.1%) target joints had no spontaneous or traumatic bleeds.
Overall, 188 (98.4%) participants experienced ≥1 adverse event (AE), with 185 treatment-related AEs occurring in 71 (37.2%) participants, with the most common treatment-related AEs reported as injection-site reactions (28.8%), headache (2.6%), rash (1.6%), itching (1.0%), and nausea (1.0%). A serious AE was reported in 44 (23.0%) participants. Additionally, two thromboembolic events were reported, and researchers indicated that these events were regarded as unrelated to emicizumab, and there were no reports of thrombotic microangiopathies.
The researchers also noted that after the trials were completed, many study participants continued using emicizumab, either via a posttrial access program or by switching to the commercial version. The authors wrote, “This is in agreement with the high proportion of participants in HAVEN 3 (94%) and HAVEN 4 (100%) who reported that they preferred emicizumab over their prior treatments when completing the EmiPref questionnaire at Week 17 of their respective study.”
Based on their findings, the authors wrote, “The final analyses of the HAVEN 3 and 4 studies provide insight into the long-term efficacy and safety of emicizumab prophylaxis in people with HA without FVIII inhibitors. The overall ABRs in both studies remained consistently low throughout long-term follow-up, with no unexpected or new safety signals observed.”
The researchers concluded, “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 HA without inhibitors, with consistent bleed prevention and no new or unexpected safety signals.”
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