OC 14.2 - Surgical experience in people with hemophilia A or B with and without inhibitors receiving fitusiran

Sunday, June 23, 2024

09:45 – 10:00 ICT

Room: Ballroom B4

Presenting Author(s)

Alok Srivastava

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

Co-Author(s)

PG

Pencho Georgiev

MD
University Multiprofile Hospital for Active Treatment “Sveti Georgi” and Medical University Plovdiv, Bulgaria
Plovdiv, Plovdiv, Bulgaria
TL

Toshko Lissitchkov

Professor
Specialized Hospital for Active Treatment of Hematological Diseases, Department of Chemotherapy, Hemotherapy and Hereditary Blood Diseases at Clinical Hematology Clinic, Sofia, Bulgaria
Sofia, Sofiya, Bulgaria
Margaret V. Ragni

Professor of Medicine and Clinical and Translational Science
Department of Medicine, University of Pittsburgh
Pittsburgh, Pennsylvania, United States
LM

Laurel A. Menapace

Lead Global Safety Officer, Rare Blood Disorders
Sanofi, Cambridge, MA, United States
Cambridge, Massachusetts, United States
YS

Yuqian Shen

Associate Statistical Project Leader
Sanofi, Bridgewater, NJ, United States
Bridgewater, New Jersey, United States
ZQ

Zhiying Qiu

Senior Biostatistics Project Leader
Sanofi, Bridgewater, NJ, United States
Bridgewater, New Jersey, United States
MP

Marja Puurunen

Senior Clinical Research Director
Sanofi, Cambridge, MA, United States
Cambridge, Massachusetts, United States
SA

Shauna Andersson

Global Clinical Lead
Sanofi, Cambridge, MA, United States
Cambridge, Massachusetts, United States
MD

Marek Demissie

Global Project Head, Rare Diseases and Rare Blood Disorders Clinical Development
Sanofi, Cambridge, MA, United States
Cambridge, Massachusetts, United States
Steven W. Pipe, MD

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

Background: Fitusiran, a subcutaneous, investigational siRNA therapeutic lowers antithrombin with the goal of increasing thrombin generation and rebalancing hemostasis in people with hemophilia (PwH) A or B, regardless of inhibitor status. For the management of perioperative hemostasis, Bleed Management Guidelines (BMG) with reduced dose and/or frequency of clotting factor concentrates (CFC) or bypassing agents (BPA) were implemented (Table).

Aims: To describe hemostatic outcomes of major surgeries conducted while on fitusiran prophylaxis in PwHA/B aged ≥12 years, regardless of inhibitor status.

Methods: All major surgeries in the fitusiran clinical development program until June 2023 were evaluated, including participants on the 80 mg QM and revised antithrombin-based dose regimen. Informed consent and ethics committee approval were obtained. Procedures conducted during fitusiran prophylaxis and AT activity < 60% were included. Major surgeries included: opening into major body cavity, operation on a joint, removal of an organ, operative alteration of normal anatomy, crossing of a mesenchymal barrier, dental extraction of molar teeth or ≥3 nonmolar teeth, or tooth implantation. Investigators/surgeon assessed peri-operative hemostatic control based on the ISTH 4-point response scale (excellent/good/moderate/poor).

Results: Sixty major surgeries (24 in inhibitor patients) were performed. In 47 (78.3%) major surgeries, BMG were followed, and reduced doses were used as perioperative prophylaxis. Four major surgeries were conducted without additional CFC/BPA. Hemostatic control on the day of the surgery was rated excellent/good in 30/31 (97%) cases following BMG and 9/10 (90%) cases not following BMG (Figure). ATIII concentrate was used to reverse the pharmacodynamic effect of fitusiran in 7 surgeries with an excellent/good hemostatic outcome. No major treatment‐related safety concerns were identified perioperatively. Postoperative thrombosis occurred only when dosing exceeded BMG recommendations in 2 participants.

Conclusion(s): Major surgeries can be safely and effectively conducted during fitusiran prophylaxis when BMG are followed, irrespective of inhibitor status. Reversal of lowered AT is not necessary.

Funding: Sanofi.