Efficacy and safety of marstacimab prophylaxis in hemophilia A/B with inhibitors: results from the phase 3 BASIS trial
Abstract
Abstract Marstacimab, a monoclonal antibody that inhibits tissue factor pathway inhibitor, is approved for prophylactic use in individuals with hemophilia A or B without inhibitors. We present efficacy and safety for individuals with inhibitors. The open-label, single-arm, phase 3 study evaluated once-weekly subcutaneous flat-dose marstacimab in males aged 12 to <75 years with severe hemophilia A or moderately severe to severe hemophilia B. Participants with inhibitors received bypassing agents (on-demand or routine prophylaxis) during a 6-month observational phase (OP) before entering a 12-month active treatment phase (ATP) with marstacimab. Primary end points were annualized bleeding rate (ABR) of treated bleeds and safety. Of 60 participants with inhibitors in the OP, 51 entered the ATP and received marstacimab. In the on-demand group (n = 48), mean estimated ABR declined from 19.78 (95% confidence interval [CI], 16.12-24.27) in the OP to 1.39 (95% CI, 0.85-2.29) during the ATP (ABR ratio, 0.07 [95% CI, 0.042-0.118]; 2-sided P< .0001). Results were consistent by hemophilia type (ABR ratio, 0.05 [hemophilia A, n = 40]; 0.13 [hemophilia B, n = 8]). Participants reported significant improvements in health-related quality of life. Adverse events were common but mostly mild; 1 treatment-related grade 3 skin rash led to discontinuation. Antidrug antibodies were detected in 19.6% of participants, with no apparent effect on efficacy or safety. In participants with inhibitors, marstacimab was associated with reduced bleeding rates and an acceptable safety profile, with no thromboembolic events. Marstacimab may be a viable treatment option for people with hemophilia A or B with inhibitors. This trial was registered at www.clinicaltrials.gov as #NCT03938792. ClinicalTrials.gov identifier: NCT03938792.
Article Details
Authors (60)
Davide Matino
Department of Medicine, McMaster University, Hamilton, ON, Canada
Suchitra S. Acharya
3Northwell Health, New Hyde Park, NY
Carrie Turich Taylor
5Pfizer Inc, Collegeville, PA
Pengling Sun
6Pfizer Inc, Cambridge, MA
Delphine Agathon
7Pfizer Inc, Paris, France
Sangeeta Raje
5Pfizer Inc, Collegeville, PA
Travis Gould
8Pfizer Inc, New York, NY
Andrew Palladino
5Pfizer Inc, Collegeville, PA
Johnny Mahlangu
Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand and National Health Laboratory Service, Johannesburg
Toshko Lissitchkov
Mariya Todorova
Anthony Chan
Manuel Carcao
Jing Sun
Renchi Yang
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Runhui Wu
Chenghao Jin
Xiaojing Zeng
Ana Boban
Ernest Bilic
Laurent Frenzel
Godfrey Chi Fung Chan
Chi Kong LI
Shashikant Apte
Nirmalkumar Choraria
Antonio Chistolini
Emanuela Marchesini
Flora Peyvandi
Teruhisa Fujii
Tadashi Matsushita
Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan
Makoto Kaneda
Chuhl Joo Lyu
Department of Pediatrics, Yonsei University Severance Hospital, Seoul, South Korea
Young Shil Park
Sungeun Kim
Laura Villarreal Martinez
Javier Morales Adrian
Yasser Wali
Murtadha Al Khabori
Igor Kurtov
Hazzaa Alzahrani
Galila Zaher
Dragan Micic
Predrag Miljic
Gordana Kostic
Miodrag Vucic
Predrag Djurdjevic
Olga Benitez Hidalgo
Jose Gonzalez Porras
Víctor Jiménez-Yuste
Jose Manuel Calvo Villas
Maria Fernanda Lopez Fernandez
Canan Albayrak
Vahap Okan
Can Balkan
Fahri Sahin
Ali Antmen
Ekrem Unal
Nathan Visweshwar
Anjali Sharathkumar
3Stead Family Department of Pediatrics, The University of Iowa, Iowa City, IA
Rebecca Kruse-Jarres