LB 01.1 - A Phase 3 study (ATLAS-PPX) to evaluate efficacy and safety of fitusiran, an siRNA therapeutic, in people with haemophilia A or B who have switched from prior factor or bypassing agent prophylaxis

Sunday, July 10, 2022

2:45 PM – 3:00 PM

Location: ICC Auditorium

Presentation Format: In-Person

Presenting Author(s)

Gili Kenet, MD

Director
The National Hemophilia Center, and Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Tel Aviv University, Tel Aviv, Israel
Yehud-Monosson, HaMerkaz, Israel

Co-Author(s)

BN

Beatrice Nolan

Consultant Hematologist
Children's Health Ireland at Crumlin
Dublin, Dublin, Ireland
Bulent Bulent Zulfikar, MD

Prof. Dr. O. Bulent Zulfikar, Pediatric Hematology and Oncology
Istanbul University Oncology Institute
Istanbul, Istanbul, Turkey
BA

Bulent Antmen

Prof. A. Bulent Antmen, MD
Department of Pediatric Hematology/Oncology and Bone Marrow Transplantation Unit, Faculty of Medicine, Acibadem University, Adana Hospital
Adana, Adana, Turkey
PK

Peter Kampmann

Consultant Specialist, Head of Leukaemia Unit
Department of Hematology, Copenhagen University Hospital, Rigshospitalet
Copenhagen, Hovedstaden, Denmark
TM

Tadashi Matsushita

Professor
Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan.
Nagoya, Aichi, Japan
CY

Chur-Woo You

Professor
Department of Pediatrics, Daejeon Eulji Medical Center, Eulji University School of Medicine, Daejeon, South Korea
Daejeon, Ch'ungch'ong-namdo, Republic of Korea
KV

Kateryna Vilchevska

Head of the NCCL Ohmatdet Hemostasis Pathology Center
“National Specialized Children's Hospital “OKHMATDYT” of the Ministry of Health of Ukraine”, Hemostasis Pathology Center
Kyiv, Kyyiv, Ukraine
Catherine N. N. Bagot, Dr MBBS MD

MD, PhD
Department of Haematology, Glasgow Royal Infirmary, Glasgow, United Kingdom
Glasgow, Scotland, United Kingdom
AS

Azizan Sharif

Hematologist
Hospital Sultanah Aminah
Johor Bahru, Johor, Malaysia
Flora Peyvandi, MD, PhD

Professor of Internal Medicine; Director of the Angelo Bianchi Bonomi Hemophilia & Thrombosis Center
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
Milan, Lombardia, Italy
Guy Young, MD

Director, Hemostasis and Thrombosis Center
Children's Hospital Los Angeles
Los Angeles, California, United States
CN

Claude Negrier

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

Ting Quan

Dr
Sanofi
Chengdu, Sichuan, China (People's Republic)
SP

Stacey Poloskey

Global Safety Office, Rare Blood Disorders
Sanofi
Cambridge, Massachusetts, United States
CS

Christian Sussebach

Clinical Research Director
Sanofi
Frankfurt, Hessen, Germany
FS

Fadi Shammas

Clinical Study Director
Sanofi
Montreal, Quebec, Canada
SA

Shauna Andersson

Global Clinical Lead
Sanofi
Cambridge, Massachusetts, United States
BM

Baisong Mei

Project head
Sanofi, Cambridge, MA, USA
Cambridge, Massachusetts, United States
KK

Kaan Kavakli

Professor
Ege Hemophilia Center, Izmir, Turkey
Izmir, Izmir, Turkey

Background: Fitusiran, a subcutaneous (SC) investigational siRNA therapeutic, targets antithrombin to rebalance haemostasis in people with haemophilia A or B (PwHA/B), irrespective of inhibitor status. In previous Phase 3 trials, once-monthly fitusiran prophylaxis significantly reduced annualised bleeding rate (ABR) in PwHA/B, with or without inhibitors versus episodic/on-demand treatment.

Aims: To evaluate the efficacy and safety of fitusiran versus prior factor/bypassing agent (BPA) prophylaxis in PwHA/B, with or without inhibitors.

Methods: This Phase 3, multinational, open-label study (NCT03549871) included males aged ≥12 years with hemophilia A or B, with or without inhibitors, who had prior factor/BPA prophylaxis. Participants continued factor/BPA prophylaxis (6 months) before switching to once-monthly 80 mg SC fitusiran prophylaxis (7 months). P</span>rimary endpoint was ABR in the factor/BPA prophylaxis period (Day-168 to Day-1) and fitusiran efficacy period (Day 29 to Day 190). Secondary endpoints included spontaneous ABR (AsBR), joint ABR (AjBR), and health-related quality of life (HRQoL). Safety and tolerability were assessed.

Results: Of 80 enrolled participants, 65 (inhibitor/non-inhibitor, n=19/46; haemophilia A/haemophilia B, n=50/15) were eligible for ABR analyses. Median observed (IQR) ABRs were 4.4 (2.2; 10.9) with factor/BPA and 0.0 (0.0; 2.3) with fitusiran prophylaxis; 41 participants (63.1%) experienced zero treated bleeds with fitusiran. Fitusiran achieved statistically significant reductions in estimated ABR, AsBR and AjBR versus factor/BPA prophylaxis (Table 1). Fitusiran significantly improved HRQoL versus factor/BPA as measured by Haem-A-QOL total score (LS mean difference -4.6 [95% CI: -7.6; -1.5; p< 0.01]). Serious adverse events (SAEs) occurred in 5/65 participants (7.7%) with factor/BPA and 9/67 (13.4%) with fitusiran prophylaxis. Two participants (3.0%) experienced suspected or confirmed thromboembolic events with fitusiran (Table 2).

Conclusion(s): Once-monthly fitusiran prophylaxis significantly reduced bleeding versus factor/BPA prophylaxis with a median ABR of zero in PwHA/B with and without inhibitors, resulting in a meaningful improvement in HRQoL. Reported AEs were generally consistent with previously identified risks of fitusiran.