OR08 - Joint health in participants with hemophilia A or B with inhibitors treated with marstacimab in the phase 3 BASIS trial
OR08
Joint health in participants with hemophilia A or B with inhibitors treated with marstacimab in the phase 3 BASIS trial
J. Mahlangu1,*, V. Jimenez-Yuste2, H. K. Kim3, T. Gould3, P. Sun4, C. Turich Taylor5, J. Healy6, T. Hinnershitz5, A. Palladino5
1Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, National Health Laboratory Service, Johannesburg, South Africa, 2Hospital Universitario La Paz-IdiPaz, Universidad Autónoma, Madrid, Spain, 3Pfizer Inc, New York, NY, 4Pfizer Inc, Cambridge, MA, 5Pfizer Inc, Collegeville, PA, United States, 6Pfizer Canada ULC, Kirkland, QC, Canada
Introduction: Patients with hemophilia A (HA) or B (HB) with inhibitors face limited prophylactic options and remain at risk of progressive joint damage. Marstacimab, a human monoclonal antibody targeting tissue factor pathway inhibitor, rebalances hemostasis independently of factor replacement. We evaluated the impact of marstacimab on joint health in participants (pts) with inhibitors in the BASIS trial (NCT03938792).
Methods: BASIS was an open-label, phase 3 study in males aged ≥12 to <75 years with severe HA (FVIII <1%) or moderately severe to severe HB (FIX ≤2%). Pts entered a 6-month observational phase (OP) with on-demand or prophylactic bypassing agents, followed by a 12-month active treatment phase (ATP) with subcutaneous (SC) marstacimab (300mg loading, 150mg once-weekly [QW] maintenance). Treated joint bleeds and treated target joint bleeds, target joints (major joints with ≥3 spontaneous bleeds over 6 months) and Hemophilia Joint Health Score (HJHS) were assessed.
Results: Of 60 pts with inhibitors (HA n=47; HB n=13; median age 23 years) in the OP, 51 received marstacimab in the ATP. At study entry, 43/60 (71.7%) pts had ≥1 target joint. In the on-demand subgroup (n=48), model-based mean (descriptive median) annualized bleeding rate (ABR) for treated joint bleeds decreased from 15.15 (11.66) in the OP to 1.10 (0.00) in the ATP (mean ratio 0.07 [95% CI 0.04, 0.14]; P<0.0001). Mean (range) target joints decreased numerically from 0.6 (0.0–4.0) in the OP to 0.0 (0.0–1.0) over 12 months in the ATP. Model-based mean (descriptive median) ABR for treated target joint bleeds declined from 6.42 (2.09) to 0.79 (0.00) (mean ratio 0.12 [95% CI 0.06, 0.25]; P=0.0001). HJHS improved modestly from baseline; total score was lower after 6 months in the ATP vs 6 months in the OP (median difference, –2.2 [95% CI –5.7, 1.4]; P=0.2341).
Discussion/Conclusion: In BASIS pts with inhibitors, marstacimab markedly reduced joint and target joint bleeding and eliminated most target joints over 12 months of treatment, with early trends toward improved HJHS. Longer-term improvements in joint health will be assessed during the BASIS open-label extension study. These findings support QW SC marstacimab as a promising prophylactic option for patients with inhibitors at risk of progressive arthropathy.
Disclosure of Interest: J. Mahlangu Grant/Research support from: BioMarin, CSL Behring, Novo Nordisk, Pfizer, Roche, Sanofi, Spark, and Vega, Consultant for: BioMarin, CSL Behring, Novo Nordisk, Roche, Takeda, Sanofi, Spark, and Vega Therapeutics, V. Jimenez-Yuste Grant/Research support from: Bayer, BioMarin, CSL-Behring, Grifols, Novo Nordisk, Octapharma, and Pfizer, Roche, Sobi, and Takeda, Consultant for: Bayer, BioMarin, CSL-Behring, Grifols, Novo Nordisk, Octapharma, and Pfizer, Roche, Sobi, and Takeda, H. K. Kim Shareholder of: Pfizer, Employee of: Pfizer, T. Gould Shareholder of: Pfizer, Employee of: Pfizer, P. Sun Shareholder of: Pfizer, Employee of: Pfizer, C. Turich Taylor Shareholder of: Pfizer, Employee of: Pfizer, J. Healy Shareholder of: Pfizer, Employee of: Pfizer, T. Hinnershitz Shareholder of: Pfizer, Employee of: Pfizer, A. Palladino Shareholder of: Pfizer, Employee of: Pfizer