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. 2024 Mar 1;8(2):102364.
doi: 10.1016/j.rpth.2024.102364. eCollection 2024 Feb.

Long-term outcomes with emicizumab in hemophilia A without inhibitors: results from the HAVEN 3 and 4 studies

Johnny Mahlangu  1 , Víctor Jiménez-Yuste  2 , Giuliana Ventriglia  3 , Markus Niggli  4 , Simona Barlera  5 , Cédric Hermans  6 , Michaela Lehle  3 , Pratima Chowdary  7 , Lyle Jew  8 , Jerzy Windyga  9 , Laurent Frenzel  10 , Christophe Schmitt  11 , Giancarlo Castaman  12 , Steven W Pipe  13
Affiliations

Long-term outcomes with emicizumab in hemophilia A without inhibitors: results from the HAVEN 3 and 4 studies

Johnny Mahlangu et al. Res Pract Thromb Haemost. .

Abstract

Background: Emicizumab, a bispecific monoclonal antibody, bridges activated factor (F) IX and FX, mimicking the function of missing or deficient activated FVIII in people with hemophilia A (HA).

Objectives: To evaluate the long-term efficacy and safety of emicizumab prophylaxis in people with HA without FVIII inhibitors in the HAVEN 3 and 4 studies.

Methods: HAVEN 3 and 4 were phase 3 open-label studies. Participants received emicizumab maintenance doses of 1.5 mg/kg every week or 3 mg/kg every 2 weeks (HAVEN 3), or 6 mg/kg every 4 weeks (HAVEN 4). Long-term efficacy and safety were assessed.

Results: A total of 151 and 40 individuals without FVIII inhibitors received emicizumab in HAVEN 3 and 4, respectively. At the last patient, last visit dates (May 12, 2022 [HAVEN 3] and June 29, 2022 [HAVEN 4]), the median (range) duration of emicizumab exposure across the 2 studies was 248.1 (6.1-287.1) weeks. The mean (95% CI) annualized bleed rate for treated bleeds was 2.0 (0.23-7.15) for weeks 1 to 24, decreasing to 0.9 (0.01-5.28) by weeks 217 to 240. Overall, 188 (98.4%) participants experienced ≥1 adverse event (AE), with 185 treatment-related AEs in 71 (37.2%) participants. Forty-four (23.0%) participants reported a serious AE. Two thromboembolic events were reported, which were deemed unrelated to emicizumab by the investigator. No thrombotic microangiopathies were reported.

Conclusion: With nearly 5 years of emicizumab exposure across the HAVEN 3 and 4 studies in people with HA without inhibitors, these data indicate continued bleed control with no new safety signals observed during long-term follow-up.

Keywords: efficacy; emicizumab; hemophilia A; prophylaxis; safety.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Participant flowchart. ∗Participants received episodic factor VIII prior to study entry; †Participants received prophylactic FVIII prior to study entry; ‡Participants received no prophylaxis until week 24, after which they were given a loading dose of emicizumab 3 mg/kg QW, followed by a maintenance dose of 3 mg/kg Q2W; §No loading dose period was included for this cohort. F, factor; HA, hemophilia A; QW, once weekly; Q2W, once every 2 weeks; Q4W, once every 4 weeks.
Figure 2
Figure 2
Mean annualized bleeding rates (ABRs) for (A) treated bleeds and (B) all bleeds over 24-week intervals.
Figure 3
Figure 3
Proportion of participants with zero treated bleeds over 24-week intervals.
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References

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