OC 30.5 - 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

Monday, July 11, 2022

11:45 AM – 12:00 PM

Location: ExCel Center, ICC Auditorium

Presentation Format: In-Person

Presenting Author(s)

Cédric Hermans, Professor

Professor, Head of Hematology
Cliniques Universitaires Saint-Luc
Brussels, Brussels Hoofdstedelijk Gewest, Belgium

Co-Author(s)

CN

Claude Negrier

Professor
Louis Pradel University Hospital, Claude Bernard University Lyon 1
Lyon, Auvergne, France
ML

Michaela Lehle

Global Development Leader, Hematology
F. Hoffmann-La Roche Ltd.
Basel, Basel-Stadt, Switzerland
Pratima Chowdary, MD

Consultant Haematologist
Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free London NHS Foundation Trust, London, United Kingdom
London, England, United Kingdom
OC

Olivier Catalani

Senior Statistical Scientist
F. Hoffmann-La Roche Ltd.
Basel, Basel-Stadt, Switzerland
Víctor Jiménez Yuste, MD PhD

Head of Hematology
La Paz University Hospital
Madrid, Madrid, Spain
BB

Benjamin M Beckermann

Senior Clinical Scientist
F. Hoffmann-La Roche Ltd.
Basel, Basel-Stadt, Switzerland
CS

Christophe Schmitt

Clinical Pharmacologist
F. Hoffmann-La Roche Ltd.
Basel, Basel-Stadt, Switzerland
GV

Giuliana Ventriglia

Lead Clinical Scientist
F. Hoffmann-La Roche Ltd.
Basel, Basel-Stadt, Switzerland
JW

Jerzy Windyga

Head Department of Hemostasis Disorders and Internal Medicine
Institute of Hematology and Transfusion Medicine
Warsaw, Mazowieckie, Poland
Anna Kiialainen, PhD

Senior Scientist
F. Hoffmann-La Roche Ltd.
Basel, Basel-Stadt, Switzerland
RD

Roseline D'Oiron

Hematologist
Haemophilia Treatment Centre, Bicêtre Hospital, University Hospital of Paris (APHP), Kremlin-Bicêtre, France.
paris, Centre, France
PM

Paul Moorehead

Pediatric Hematologist/Oncologist
Memorial University of Newfoundland
St John’s, Newfoundland and Labrador, Canada
SK

Sunita Koparkar

Safety Science Director
Genentech, Inc.
San Francisco, California, United States
VT

Vanda Teodoro

Senior Patient-Centered Outcomes Research Scientist
F. Hoffmann-La Roche Ltd.
Basel, California, United States
AS

Amy Shapiro

Medical Director
Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA
Indianapolis, Indiana, United States
JO

Johannes Oldenburg

Director of the Institute of Experimental Haematology and Transfusion Medicine
University Clinic Bonn, Institute of Experimental Haematology and Transfusion Medicine, Bonn, Germany
Bonn, Berlin, Germany

Background: Emicizumab is a bispecific monoclonal antibody that substitutes for missing activated factor (F)VIII in people with hemophilia A (HA).

Aims: This primary analysis of HAVEN 6 (NCT04158648) aims to assess safety and efficacy of emicizumab prophylaxis in people with non-severe HA without FVIII inhibitors.

Methods: 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).

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.

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