Efficacy and safety of marstacimab prophylaxis in hemophilia A/B with inhibitors: results from the phase 3 BASIS trial.
СтатьяКлиническое исследование III фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Matino Davide, Acharya Suchitra S, Taylor Carrie Turich, Sun Pengling, Agathon Delphine, Raje Sangeeta, Gould Travis, Palladino Andrew, Mahlangu Johnny, Lissitchkov Toshko, Todorova Mariya, Chan Anthony, Carcao Manuel, Sun Jing, Yang Renchi, Wu Runhui, Jin Chenghao, Zeng Xiaojing, Boban Ana, Bilic Ernest, Frenzel Laurent, Fung Chan Godfrey Chi, Kong Li Chi, Apte Shashikant, Choraria Nirmalkumar, Chistolini Antonio, Marchesini Emanuela, Peyvandi Flora, Fujii Teruhisa, Matsushita Tadashi, Kaneda Makoto, Lyu Chuhl Joo, Park Young Shil, Kim SungEun, Martinez Laura Villarreal, Adrian Javier Morales, Wali Yasser, Al Khabori Murtadha, Kurtov Igor, Alzahrani Hazzaa, Zaher Galila, Micic Dragan, Miljic Predrag, Kostic Gordana, Vucic Miodrag, Djurdjevic Predrag, Hidalgo Olga Benitez, Porras Jose Gonzalez, Jiménez-Yuste Víctor, Calvo Villas Jose Manuel, Lopez Fernandez Maria Fernanda, Albayrak Canan, Okan Vahap, Balkan Can, Sahin Fahri, Antmen Ali, Unal Ekrem, Visweshwar Nathan, Sharathkumar Anjali, Kruse-Jarres Rebecca
Аннотация
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.