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716 Descriptive Characterization of Bleeding Events in Participants with Severe Hemophilia Α or B without Inhibitors, Receiving Prophylactic Marstacimab Treatment

Program: Oral and Poster Abstracts
Type: Oral
Session: 322. Hemophilia A and B: Clinical and Epidemiological: Impact of Novel Therapies on Outcomes, Including Long-Term
Hematology Disease Topics & Pathways:
Research, Clinical trials, Bleeding and Clotting, Hemophilia, Clinical Research, Diseases
Monday, December 9, 2024: 10:45 AM

Davide Matino, MD, MSc1*, Travis Gould, PhD2, John Teeter, MD3*, Carrie Turich Taylor, PhD, MHS3*, Regina McDonald, BSN2* and Andrew Palladino, MD4*

1McMaster University, Hamilton, ON, Canada
2Pfizer Inc, New York, NY
3Pfizer Inc, Groton, CT
4Global Clinical Lead for the Marstacimab Program at Pfizer, Pfizer, Collegeville, PA

Background:

Marstacimab is a monoclonal antibody targeted to the K2 domain of tissue factor pathway inhibitor to reduce inhibition of the extrinsic coagulation pathway and rebalance hemostasis independently of factor VIII (FVIII) and factor IX (FIX) activity. Previous phase 1 and 2 studies have demonstrated the efficacy and safety of subcutaneous (SC) marstacimab prophylaxis up to 450 mg once weekly (QW) to reduce bleeding events in adults with hemophilia A (HA) or hemophilia B (HB), with or without inhibitors. The ongoing pivotal phase 3 BASIS study (NCT03938792) demonstrated 150 mg SC QW marstacimab was effective in reducing treated bleeds vs prior on-demand (OD) or routine prophylaxis (RP) therapy in participants (pts) with severe HA (FVIII <1%) or moderately severe to severe HB (FIX ≤2%) without inhibitors. Contemporary hemophilia trials typically report treated bleeding events as the primary endpoint to determine the efficacy of prophylactic treatment. As such, untreated bleeding episodes are often underreported. It is important to consider both treated and untreated bleeding events to understand overall bleed management. We describe the characteristics of treated and untreated bleeding events in the BASIS study.

Methods:

BASIS enrolled male pts aged ≥12 to ˂75 years with severe HA or moderately severe to severe HB, with or without inhibitors. Results are reported for the non-inhibitor cohort; the inhibitor cohort is ongoing. Pts entered a 6-month observational phase (OP) and received their prescribed factor replacement therapy (OD or RP) before crossing over to the 12-month active treatment phase (ATP) to receive a single loading dose of 300 mg marstacimab (2x150 mg SC) followed by 150 mg SC QW. The incidence of bleeding episodes, including etiology (spontaneous, traumatic, or procedural), location (joint or soft tissue/muscle), and whether treatment was required (intravenous coagulation factor products or bypass agents) were obtained from pt diaries and medical records. Bleed data were collected over 6 months for the OP phase and 12 months for the ATP phase. Descriptive data are presented.

Results:

In total, 128 pts (median age 30 [range 13-66] years) entered the 6-month OP (n: OD: HA 29, HB 8; RP: HA 72, HB 19) and 116 (n: OD 33, RP 83) continued to the 12-month ATP. At baseline, 89 (69.5%) pts (OD: n=36; RP: n=53) had ≥1 target joint. The mean (range) duration of marstacimab treatment was 12.1 (11.5-13.1) months for the OD group and 11.6 (0.9-12.8) months for RP group. Of 116 pts, 88 (75.9%; OD 33 [100%], RP 55 [66.3%]) experienced ≥1 bleeding event during the 6-month OP and 85 (73.3%; OD 29 [87.9%], RP 56 [67.5%]) during the 12-month ATP. The total number of bleeding events during the 6-month OP was 1312 (n: OD 899 [68.5%]; RP 413 [31.5%]), of which 1114 (84.9%) were treated (OD 83.3%; RP 88.4%). The total number of bleeding events during the 12-month ATP was 687 (n: OD 243 [35.4%]; RP 444 [64.6%]), of which 504 (73.4%) were treated (OD 48.6%; RP 86.9%). The majority of bleeding episodes were spontaneous in both the OD (OP 83.4%; ATP 77.4%) and RP (OP 72.4%; ATP 70.5%) groups. In both groups, most bleeds occurred in joints (OP: OD 84.0%, RP 62.5%; ATP: OD 82.3%, RP 71.6%) than in soft tissue/muscle (OP: OD 13.0%, RP 32.2%; ATP: OD 13.2%, RP 25.9%). The most common sites of joint bleeds were the ankle/foot, elbow, and knee for both groups in the OP and ATP.

Conclusions:

The majority of bleeds across both OD and RP groups during the BASIS study (OP and ATP) were spontaneous, treated, and occurred in joints, most commonly the ankle/foot, elbow, and knee. In the OD group, marstacimab prophylaxis resulted in a greater proportion of pts without any bleeding events and a lower proportion with treated bleeds during the ATP vs the OP. Of pts who had bleeding events, the RP group had a relatively greater proportion of treated bleeds (86.9%) vs the OD group (48.6%). Of note, in pts with prior FVIII prophylaxis in the HAVEN-3 emicizumab study who had bleeds, 24% of total bleeds were treated (Callaghan et al, RPTH, 2022), suggesting differences in bleed management vs the BASIS study. Overall, these results demonstrate that a high proportion of bleeding events were treated with factor replacement therapy in the BASIS study, but that clinical management and treatment strategies may differ across trials.

Disclosures: Matino: Roche: Research Funding; Octapharma: Honoraria, Other: Scientific Advisory Board, Research Funding, Speakers Bureau; Bayer: Consultancy, Honoraria, Other: Scientific Advisory Board, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Other: Scientific Advisory Board, Research Funding, Speakers Bureau; Novo Nordisk: Honoraria, Other: Scientific Advisory Board, Research Funding, Speakers Bureau; Sanofi: Honoraria, Other: Scientific Advisory Board, Research Funding, Speakers Bureau; Spark: Research Funding; Sobi: Honoraria, Other: Scientific Advisory Board, Speakers Bureau. Gould: Pfizer: Current Employment, Current equity holder in publicly-traded company. Teeter: Pfizer: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Taylor: Pfizer: Current Employment, Current equity holder in publicly-traded company. McDonald: Pfizer: Current Employment, Current equity holder in publicly-traded company. Palladino: Pfizer: Current Employment, Current equity holder in publicly-traded company.

*signifies non-member of ASH