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1240 Experience with Emicizumab Among People with Hemophilia A in the Canadian Hemophilia Bleeding Disorders Registry

Program: Oral and Poster Abstracts
Session: 322. Disorders of Coagulation or Fibrinolysis: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
bleeding disorders, Biological therapies, Bleeding and Clotting, Research, hemophilia, Bispecific Antibody Therapy, Clinical Research, Diseases, Therapies, real-world evidence
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Man-Chiu Poon1, Adrienne Lee2, Federico Germini3*, Arun Keepanasseril3*, Quazi Ibrahim3*, Letizia Polito4*, Katya Moreno4*, Michelle Santos5*, Emma Iserman3*, Davide Matino, MD6* and Alfonso Iorio, MD, PhD7

1University of Calgary, Calgary, AB, Canada
2University of British Columbia, Victoria, BC, Canada
3McMaster University, Hamilton, ON, Canada
4F. Hoffmann-La Roche Ltd, Basel, Switzerland
5F. Hoffmann-La Roche Ltd, Mississauga, ON, Canada
6Thrombosis and Atherosclerosis Research Institute (TaARI), Hamilton, ON, Canada
7Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada

Background: The use of emicizumab as prophylaxis to prevent bleeding or reduce the frequency of bleeding episodes in congenital hemophilia A (HA) was approved by Health Canada for the treatment of people living with HA (PwHA) with FVIII inhibitors in 2018, and without inhibitors in 2019.

Here we present the results of a non-interventional, cohort study, using data routinely collected by the Canadian Bleeding Disorders Registry (CBDR) to evaluate treatment patterns of emicizumab in Canada and the associated safety and effectiveness outcomes, including quality of life.

Methods: De-identified data were extracted from the CBDR database for all registered PwHA who had received emicizumab at least once prior to December 31, 2022. Baseline demographic characteristics were stratified by disease severity (defined by the level of endogenous FVIII activity) and age. Effectiveness outcomes were measured by the proportion of patients with zero, traumatic, spontaneous, or joint bleeds as well as annualized bleeding rates (ABR) for any treated bleed. Intra-patient comparisons of bleeding were performed for all patients and for those with at least six months follow-up in both pre- and post-emicizumab periods as a sensitivity analysis. Effectiveness outcomes also included patients’ Hemophilia Joint Health Score (HJHS), Patient Reported Outcomes, Burdens and Experiences (PROBE), and EQ-5D index and visual analog scale (VAS) scores. We performed a complete data analysis, without imputation. This study was approved by the research ethics board of McMaster University and other participating centers, and abides by the guiding principles of the Declaration of Helsinki.

Results: In total, 533 PwHA received at least one dose of emicizumab (PwHAE) in the CBDR database. Overall, 498 (93.4%) PwHAE had severe disease, 28 (5.3%) had moderate disease, and 7 (1.3%) had mild disease. At start of emicizumab exposure, 220 (41.3%) PwHAE were <18 years old; 78 (14.6%) PwHAE had current FVIII inhibitors, 82 (15.4%) had a history of FVIII inhibitors, and 373 (70%) had no history of inhibitors (Table 1).

A total of 13 adverse events were reported in the entire observation period, including one event of thrombosis (occurring in one person with COVID-19), seven allergic reactions, two FVIII Inhibitor development, two neurological events (headache; and headache, nausea, and vomiting) and one case of large hematoma developed at operative site following removal of port-a-cath. Moreover, nine COVID-19 cases were reported as adverse events.

Over a median (first quartile, third quartile) follow-up time of 249 (136, 395) days, 388 (72.8%) PwHAE had no recorded bleeds. Out of 145 PwHAE with recorded bleeds, 106 had joint bleeds, 87 had traumatic bleeds, 69 had spontaneous bleeds and 46 had other bleeds (Table 2).

An intra-patient comparison in all PwHAE (n=533) showed a decrease in mean (95% confidence interval [CI]) annualized bleeding rate (ABR) from 1.22 (1.06, 1.42), pre-emicizumab (2018, prior to first dose) to 0.50 (0.41, 0.60) post-emicizumab (rate ratio (95% CI) 0.41 (0.33, 0.50), p-value <0.001). The Intra-patient comparison in PwHAE without current inhibitor (n=455) showed a decrease in mean ABR (95% CI) from 1.02 (0.87, 1.19) to 0.54 (0.44, 0.66) (rate ratio (95% CI) 0.53 (0.43, 0.65), p-value <0.001). The Intra-patient comparison in PwHAE with current inhibitor (n=78) showed a decrease in mean ABR (95% CI) from 5.03 (3.30, 7.66) to 0.41 (0.26, 0.65) (rate ratio (95% CI) 0.08 (0.04, 0.15), p-value <0.001).

Conclusions: This analysis describes the baseline characteristics, safety and effectiveness outcomes of Canadian PwHA treated with emicizumab before December 31, 2022. A total of 387 new patients were included in this analysis compared to the previous one (data cut: December 31, 2021, n=146). The data shows that 72.8% PwHAE had no recorded bleeds since they started emicizumab and that there was a substantial decrease in bleeds post-emicizumab in both PwHA with and without current FVIII inhibitor. The safety profile of emicizumab was consistent with previous reports. The CBDR allows for a longitudinal follow-up of the Canadian hemophilia A population, which can inform healthcare practitioners and regulatory authorities of the safety and efficacy outcomes of treatments in routine clinical practice.

Disclosures: Poon: University of Calgary: Current Employment; KVR Pharma, Novo Nordisk, Octapharma, Sobi, Takeda: Honoraria. Lee: Pfizer, Novo Nordisk, Leo Pharma, Bayer, Takeda: Honoraria; Takeda: Speakers Bureau. Germini: Canadian Association of Emergency Physicians: Honoraria; Novo Nordisk, Roche, Takeda, Bayer, Pfizer, BioMarin: Other: Research funding as a co-investigator: institution received research funds from:; Canadian Venous Thromboembolism and Outcomes Research (CanVECTOR); - Hamilton Health Sciences (HHS): Research Funding; McMaster University: Current Employment, Ended employment in the past 24 months. Ibrahim: McMaster University: Current Employment. Polito: F. Hoffmann-La Roche Ltd: Current Employment; Roche Holding: Current equity holder in private company. Moreno: F. Hoffmann-La Roche Ltd: Current Employment. Santos: F. Hoffmann-La Roche Ltd: Current Employment; University of Toronto: Honoraria. Iserman: McMaster University: Current Employment. Iorio: McMaster University: Current Employment; McMaster University, Bayer, Novo Nordisk, Sanofi, Roche, Pfizer: Research Funding; WAPPS-Hemo: Patents & Royalties; Florio Medical Advisory Board, WFH Advisory Board: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH