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877 Fitusiran Treatment Impacts on Health-Related Quality of Life in Subjects with Hemophilia A and B with Inhibitors Assessed with the Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL)

Program: Oral and Poster Abstracts
Session: 322. Disorders of Coagulation or Fibrinolysis: Poster I
Hematology Disease Topics & Pathways:
Hemophilia, Adult, Diseases, Bleeding and Clotting, Non-Biological, Therapies, coagulant drugs, Study Population, Clinically relevant
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Sylvia Von Mackensen1*, Pratima Chowdary2*, Sarah Mangles3*, Qifeng Yu4*, Baisong Mei4, Shauna R. Andersson4* and Pronabesh Dasmahapatra, MBBS, MPH4*

1Department of Medical Psychology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
2Katharine Dormandy Haemophilia and Thrombosis Centre Unit, Royal Free Hospital, London, United Kingdom
3Haemophilia, Haemostasis and Thombosis Centre, Basingstoke and North Hampshire Hospital, Basingstoke, United Kingdom
4Sanofi, Cambridge, MA


Fitusiran, an investigational RNA interference treatment for people with hemophilia A or B (PwH), with or without inhibitors, has shown dose-dependent lowering of antithrombin, increase in thrombin generation, and decrease in bleeding frequency in clinical trials. The novel mechanism of action and long pharmacodynamic effect enables once-monthly subcutaneous administration. This sustained hemostatic protection and less burdensome administration may improve patient-reported outcomes (PRO).


To evaluate changes in PRO in terms of patient-relevant improvements in health-related quality of life (HRQoL) in PwH with inhibitors (PwHI) on prophylactic fitusiran treatment.


Fitusiran was evaluated in a phase 1 dose-escalation study (NCT02035605) followed by a phase 2 open-label extension (OLE) study (NCT02554773) with monthly subcutaneous fixed doses of 50 mg or 80 mg. HRQoL was assessed using the Haem-A-QoL and the EuroQol 5 Dimensions (EQ-5D) questionnaires at baseline and at end of study in a cohort of 17 PwHI (Hemophilia A, n=15; Hemophilia B, n=2) from the phase 1 study.


Subjects previously treated on-demand or prophylactically had a mean (standard deviation [SD]) age of 34.6 (10.3) years and a mean (SD) number of bleeding episodes in the 6 months before baseline of 16.6 (10.7). Mean (SD) changes from baseline to end of study (day 84 or later) in Haem-A-QoL total (–9.2 [11.2]) and physical health (−12.3 [15.1]) domain scores suggest clinically meaningful improvement (lower scores indicate better HRQoL). Numeric reduction (i.e., improvement) in all other domains appeared to be dose-dependent (greater improvement in the 80 mg group) (Table 1). Changes in EQ-5D utility and EQ-VAS scores were not clinically meaningful. Further analyses in PwH with and without inhibitors from the phase 2 OLE will be presented.


Fitusiran prophylaxis may improve HRQoL - particularly the Haem-A-QoL ’Physical health’ domain (painful swelling, joint pain, pain with movement, difficulty walking, and time to get ready) as shown in a cohort of 17 PwHI . Additional analyses from ongoing OLE and phase 3 studies are planned to quantify the patient-relevant changes with fitusiran treatment in all hemophilia patients over time.

Disclosures: Von Mackensen: Sanofi, Bayer, Sobi, Chugai, Kedrion, Spark: Consultancy; Biotest, Sobi, CSL Behring: Honoraria; Novo Nordisk, Sobi: Research Funding. Chowdary: BioMarin: Honoraria; Bayer, CSL Behring, Freeline, Novo Nordisk, Pfizer and Sobi: Research Funding; Chugai, CSL Behring, Novo Nordisk, Pfizer, Roche, Sobi: Speakers Bureau; Bayer, Chugai, CSL Behring, Freeline, Novo Nordisk, Pfizer, Roche, Sanofi, Shire (Baxalta), Sobi, Spark: Membership on an entity's Board of Directors or advisory committees. Mangles: Roche, Takeda, Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sobi, Octapharma, Novo Nordisk, Shire and Roche/Chugai: Other: travel funding. Yu: Sanofi: Other: was an employee and stockholder of Sanofi, at the time of study; Albireo Pharmaceuticals, Inc: Current Employment. Mei: Sanofi: Current Employment, Current equity holder in publicly-traded company. Andersson: Sanofi: Current Employment, Current equity holder in publicly-traded company. Dasmahapatra: Sanofi: Current Employment, Current equity holder in publicly-traded company.

*signifies non-member of ASH