Efficacy and safety of marstacimab prophylaxis in hemophilia A/B with inhibitors: results from the phase 3 BASIS trial
Davide Matino, Suchitra S. Acharya, Carrie Turich Taylor, Pengling Sun, Delphine Agathon, Sangeeta Raje, Travis J. Gould, Andrew Palladino, Johnny Mahlangu, Toshko Lissitchkov, Mariya Todorova, Anthony Chan, Manuel Carcao, Jing Sun, Renchi Yang, 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, Makoto Kaneda, Chuhl Joo Lyu, 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, Rebecca Kruse-Jarres
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.