OC 40.3 - Consumption of On-demand Factor Concentrates and Bypassing Agents for Management of Breakthrough Bleeds with Fitusiran Prophylaxis in People with Haemophilia A or B: An Analysis of Two Phase 3 Studies

Monday, July 11, 2022

3:15 PM – 3:30 PM

Location: ExCel Center, ICC Auditorium

Presentation Format: In-Person

Presenting Author(s)

Alok Srivastava, MD, FRACP, FRCPA, FRCP

Professor of Medicine
Christian Medical College, Vellore, India
Vellore, Tamil Nadu, India

Co-Author(s)

RW

Runhui Wu

Director and Physician in Chief
Beijing Children’s Hospital, Capital Medical University, Beijing, China
Beijing, Beijing, China (People's Republic)
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
KK

Kaan Kavakli

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

Jose Bartelt-Hofer

Senior Project Lead (Rare Blood Disorders)
Sanofi Genzyme, Chilly-Mazarin, France
Chilly-Mazarin, Ile-de-France, France
RR

Ricardo Rosim

Market Access and Strategic Pricing Director, International Markets
Sanofi Genzyme, São Paulo, Brazil
São Paulo, Sao Paulo, Brazil
ZQ

Zhiying Qiu

Biostatistics Project Leader, Associate Director
Sanofi, Bridgewater, NJ, USA
Bridgewater, New Jersey, United States
VC

Viridiana Cano

Senior Global Medical Director
Sanofi Genzyme, Cambridge, MA, USA
Cambridge, Massachusetts, United States
SA

Shauna Andersson

Global Clinical Lead
Sanofi
Cambridge, Massachusetts, United States
Steven W. Pipe, MD

Professor of Pediatrics and Pathology
University of Michigan, Ann Arbor, MI, USA
Ann Arbor, Michigan, United States

Background: Fitusiran, an investigational siRNA prophylactic, targets antithrombin mRNA to rebalance haemostasis in people with haemophilia A or B (PwHA/B), irrespective of inhibitor status. For PwHA/B receiving fitusiran, reduced doses of on-demand clotting factor concentrates (CFC) or bypassing agents (BPA) are recommended to treat breakthrough bleeds.

Aims: To explore BPA/CFC consumption with fitusiran prophylaxis vs on-demand BPA/CFC in PwHA/B, with or without inhibitors.

Methods: Two randomised, open-label, Phase 3 trials (NCT03417102 and NCT03417245) enrolled males ≥12 years with severe haemophilia A/B with inhibitors (ATLAS-INH) and without (ATLAS-A/B). Eligible participants were randomised 2:1 to once-monthly 80 mg subcutaneous fitusiran or on-demand BPA (ATLAS-INH) or CFC (ATLAS-A/B) for 9 months. Annualised weight-adjusted BPA/CFC consumption, numbers of treated bleeds and infusions per bleed were assessed.

Results: Overall, 118 participants were randomised to fitusiran, 19 to on-demand BPA and 40 to on-demand CFC. Total consumption of aPCC and rFVIIa was 97.5% and 98.2% lower in the fitusiran arm vs on-demand BPA arm; overall mean consumption of FVIII and FIX was lower in the fitusiran arm vs on-demand CFC arm (95.9% and 94.7%, respectively) (Table 1). Total number of treated bleeds were lower in the fitusiran arm vs the on-demand BPA and CFC arms by 82.0% and 79.2%, respectively. In ATLAS-INH, participants who received fitusiran required fewer mean injections (1.2 vs 3.7) and lower mean BPA doses per bleed vs participants who received on-demand BPA (Table 2). In ATLAS-A/B, participants in both arms required a mean 1.2 injections per bleed; participants who received fitusiran required lower mean CFC doses vs participants who received on-demand CFC (Table 2).

Conclusion(s): Fitusiran prophylaxis reduced total BPA/CFC consumption by reducing number of treated bleeds, number of injections and BPA/CFC doses required to treat breakthrough bleeds in PwHA/B with and without inhibitors, by ~95% or more thereby reducing treatment burden.