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

Conflict of Interest

CH has received research funding from Bayer, Shire/Takeda, Pfizer, Novo Nordisk, CSL Behring, and Sobi; honoraria and speaker’s bureau from Bayer, Shire/Takeda, Pfizer, Novo Nordisk, CSL Behring, Octapharma, Sobi, LFB, CAF-DCF, F. Hoffmann-La Roche Ltd., UniQure, and Bio Marin; CN has served as a consultant to BioMarin, Novo Nordisk, F. Hoffmann-La Roche Ltd. / Genentech, Inc., Sanofi, Sobi, and Shire/Takeda; has received research funding from Novo Nordisk, F. Hoffmann-La Roche Ltd. / Genentech, Inc., Sanofi, and Sobi; honoraria from Bayer, Novo Nordisk, F. Hoffmann-La Roche Ltd. / Genentech, Inc., Sanofi, Sobi, Spark, and Shire/Takeda; and has been a member of an entity’s Board of Directors or advisory committees for Bayer, BioMarin, CSL Behring, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd. / Genentech, Inc., Sanofi, Sobi, Spark, Shire/Takeda, and UniQure; ML is an employee and holds stock in F. Hoffmann-La Roche Ltd.; PC has served on advisory boards for Bayer, Boehringer Ingelheim, CSL Behring, Chugai, Freeline, NovoNordisk, Pfizer, Roche, Sanofi, Spark, Sobi and Takeda; and has received research funding from Bayer, CSL Behring, Freeline, Novo Nordisk, Pfizer, SOBI and Takeda; OC is an employee of F. Hoffmann-La Roche Ltd.; VJY received grant/research support from Grifols, Novo Nordisk, F. Hoffmann-La Roche Ltd, Takeda, Bayer, CSL Behring, Pfizer, consultancy fees from Grifols, Novo Nordisk, F. Hoffmann-La Roche Ltd., Takeda, Bayer, CSL Behring, Pfizer, and BioMarin; BMB is an employee and stockholder in F. Hoffmann-La Roche Ltd; CS is an employee and stockholder in F. Hoffmann-La Roche Ltd., and is co-inventor of a patent related to an anti-FIXa/FX bispecific antibody; GV is employee and stockholder in F. Hoffmann-La Roche Ltd.; JW is an employee at Institute of Hematology and Transfusion Medicine; received research funding from Baxalta, Novo Nordisk, Rigel Pharmaceuticals, F. Hoffmann-La Roche Ltd, Shire and Takeda; honoraria from Alfasigma, Bayer AG, Baxalta, CSL Behring, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche Ltd, Sanofi-Aventis, Shire, Sobi, Swixx BioPharma, Takeda and Werfen; AK is an employee of and stockholder in F. Hoffmann-La Roche Ltd.; RD received research funding from Shire, Takeda, CSL Behring, LFB, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche Ltd, Biomari, Sobi and Sanofi; honoraria: Shire, Takeda, CSL Behring, LFB, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche Ltd, Biomarin, Sobi, Sanofi, UniQure and Spark; PM holds membership on an entity's Board of Directors or advisory committees for F. Hoffmann-La Roche Ltd Canada and Bayer; SK is an employee of Genentech, Inc.; VT is employee of F. Hoffmann-La Roche Ltd.; AS is an employee of Indiana Hemophilia and Thrombosis Center, Inc.; received consultancy fees from Sangomo Biosciences, Prometic Life Sciences, Sigilon; research funding from Bioverativ, Sanofi, Genentech, Inc., Kedrion Biopharma, Novo Nordisk, Pfizer, Sigilon, Takeda, ProMetic Life Sciences and Freeline; honoraria from Genentech, Inc., Sigilon, Novo Nordisk, Pfizer and Catalyst Biosciences; speaker's bureau from Genentech, Inc., Novo Nordisk; membership on an entity's Board of Directors or advisory committees for Novo Nordisk Hemophilia Foundation, Genentech, Inc., Sigilon, Novo Nordisk and Sanofi; JO has received research funding from Bayer, Biotest, CSL Behring, Octapharma, Pfizer, Swedish Orphan Biovitrum, and Takeda; consultancy, speakers bureau, honoraria, scientific advisory board, and travel expenses from Bayer, Biogen Idec, BioMarin, Biotest, Chugai Pharmaceutical Co., Ltd., CSL Behring, Freeline, Grifols, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche Ltd., Sanofi, Spark Therapeutics, Swedish Orphan Biovitrum, and Takeda

Publication History

Article published online:
20 February 2023