Emicizumab prophylaxis for the treatment of people with moderate or mild Hemophilia A without Factor VIII inhibitors: results from the primary analysis of the HAVEN 6 study

Introduction Emicizumab is a bispecific monoclonal antibody that substitutes for missing activated factor (F)VIII in people with hemophilia A (HA). This primary analysis ofHAVEN 6 (NCT04158648) aims to assess safety and efficacy of emicizumab prophylaxis in people with non-severe HA without FVIII inhibitors.

Method HAVEN 6 is a Phase III, open-label study of emicizumab in people with moderate or mild HA without FVIII inhibitors who warrant prophylaxis as assessed by Investigator. Informed consent and ethics approval were obtained. Participants received subcutaneous emicizumab 3mg/kg weekly for 4 weeks, then 1.5mg/kg weekly, 3mg/kg every 2 weeks, or 6mg/kg every 4 weeks. Safety endpoints include adverse events (AEs), serious AEs (SAEs) and AEs of special interest, including thromboembolic events (TEs) and thrombotic microangiopathies (TMAs). Efficacy endpoints include negative binomial regression model estimates of annualized bleed rates (ABRs) ([Tab. 1]).

Tab. 1  Efficacy Summary of the HAVEN 6 study.

Results As of 30-Oct-2021, 72 participants (70.8% [n=51] moderate; 29.2% [n=21] mild; 95.8% [n=69] male; 4.2% [n=3] female) received emicizumab. Median follow-up was 55.6 weeks. At baseline, 37 participants (51.4%) were on FVIII prophylaxis; 24 (33.3%) had target joints. Within 24 weeks prior to study entry, participants had a median (range) of 2.0 (0–96) bleeds and a model-based ABR (95% CI) of 10.1 (6.93–14.76). Sixty participants (83.3%) had ≥1 AE and 15 (20.8%) had ≥1 emicizumab-related AE; no AEs led to treatment withdrawal/modification/interruption (Table 1). Ten SAEs were reported by eight participants (11.1%), none emicizumab-related. There were no deaths or TMAs. One participant experienced a Grade 1 thrombosed hemorrhoid unrelated to emicizumab, classified as a TE. Model-based ABRs (95% CI) were 0.9 (0.55–1.52) for treated bleeds, and 2.3 (1.67–3.12) for all bleeds (Table 2). Forty-eight participants (66.7%) had zero treated bleeds ([Tab. 2]).

Tab. 2  Safety Summary of the HAVEN 6 study.

Conclusion These data show continued efficacy and a favorable safety profile of emicizumab in people with non-severe HA without FVIII inhibitors who warrant prophylaxis

Publication History

Article published online:
20 February 2023