ASH 2020: Efficacy and Safety of Emicizumab in Long-term Follow-up
At the virtual meeting of the American Society of Hematology (ASH) in December 2020, the latest data concerning the long-term follow-up of participants in the HAVEN 1−4 clinical trials with emicizumab were published.
Introduction
Emicizumab, a monoclonal bispecific humanized antibody, enables effective hemostasis in patients with hemophilia A (HA). Efficacy and safety data for this drug have already been published, but long-term results were not yet available. Current findings provided pooled information regarding patients with hemophilia A with or without an inhibitor, who were monitored in the HAVEN 1−4 studies.
4 Studies − 400 Participants: Characteristics of the Study Population
The HAVEN program included pediatric and adult patients with HA. Across these studies, emicizumab was administered in maintenance doses once a week, once every two weeks, or once every four weeks. Data from 400 individuals with HA were included in the analysis, with a total treatment duration of 970.3 patient-years. The median age of patients at study entry was 28.5 years (range 1−77), 52.3% had an inhibitor to FVIII. In the last 24 weeks before study entry, 60.9% of participants had a target joint. The median duration of the treatment period was 120.4 weeks (interquartile range [IQR] 89.0−164.4), with 85% of participants being monitored for at least 74 weeks. 11 participants discontinued therapy.
Long-term Efficacy
Across all studies, the annualized bleeding rate (ABR) of treated bleeds was 1.4 (95% confidence interval [CI] 1.1−1.7), consistently remaining low with a trend towards further reduction with ongoing treatment. During weeks 121−144, 82.4% of the 170 monitored patients experienced zero treated bleeds, and 15.3% had 1−3 treated bleeds. In the same period, 91.8% of participants had zero treated spontaneous bleeds, and 90% had zero treated joint bleeds. The proportion of participants with a target joint decreased from 60.9% in weeks 1−24 to 4.6%, and then to <1.5% in subsequent intervals.
Long-term Safety
Emicizumab was well-tolerated, with no additional patients discontinuing treatment due to adverse events. As of the data cut-off in May 2020, there was one death, three cases of thrombotic microangiopathy (TMA), and four thromboembolic events − all except one occurred in the HAVEN 1 study. All TMAs and thromboembolic events were associated with the concomitant administration of aPCC.
Conclusion
In nearly three years of follow-up, emicizumab demonstrated a low bleeding rate in HA patients, regardless of age and the presence of an FVIII inhibitor. The ABR continued to decrease, and the proportion of hemophiliacs with zero treated bleeds increased with each subsequent 24-week period. A similar trend was observed for zero joint bleeds. Emicizumab also proved to be a well-tolerated drug in long-term follow-up, with no new safety signals emerging.
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Source: Callaghan M. U., Négrier C., Paz-Priel I. et al. Safety and efficacy of emicizumab in persons with hemophilia A with or without FVIII inhibitors. Pooled data from four phase III studies (HAVEN 1−4). Abstract 1800. 62nd ASH Annual Meeting and Exposition, 2020 Dec 5. Blood 2020; 136 (Suppl. 1): 3−5, doi: 10.1182/blood-2020-137438.
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