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Clinical Trial
. 2025 Oct 2;146(14):1654-1663.
doi: 10.1182/blood.2024027468.

Marstacimab prophylaxis in hemophilia A/B without inhibitors: results from the phase 3 BASIS trial

Davide Matino  1   2 , Andrew Palladino  3 , Carrie Turich Taylor  4 , Eunhee Hwang  3 , Sangeeta Raje  3 , Satyaprakash Nayak  5 , Regina McDonald  4 , Suchitra S Acharya  6 , Johnny Mahlangu  7 , Victor Jiménez-Yuste  8 , Nirmalkumar Choraria  9 , Renchi Yang  10 , Chi-Kong Li  11 , Murtadha Al-Khabori  12   13 , Yasser Wali  12   13 , Javier Morales Adrián  14 , Young-Shil Park  15 , O Bülent Zülfikar  16 , John Teeter  17
Affiliations
Clinical Trial

Marstacimab prophylaxis in hemophilia A/B without inhibitors: results from the phase 3 BASIS trial

Davide Matino et al. Blood. .

Abstract

Marstacimab targets the tissue factor pathway inhibitor to rebalance hemostasis. Previous phase 1 and 2 trials established marstacimab safety and efficacy in adults with severe hemophilia A (HA) or B (HB). BASIS is an open-label, marstacimab phase 3 trial in males aged 12 to 74 years with severe HA (factor VIII <1%) or moderately severe to severe HB (factor IX ≤2%). Participants without inhibitors received on-demand (OD) or routine prophylaxis (RP) therapy during a 6-month observational phase (OP) before receiving once-weekly subcutaneous 150 mg marstacimab during a 12-month active treatment phase (ATP). Primary end points were annualized bleeding rate (ABR) for treated bleeds vs previous OD or RP during the OP, and safety. Of 128 participants enrolled in the OP, 116 received marstacimab in the ATP. In the OD group (n = 33), mean ABR decreased from 39.86 (95% confidence interval [CI], 33.05-48.07) in the OP to 3.20 (95% CI, 2.10-4.88) in the ATP, demonstrating superiority of marstacimab (estimated ABR ratio, 0.080 [95% CI, 0.057-0.113]; P < .0001). In the RP group (n = 83), mean ABR decreased from 7.90 (95% CI, 5.14-10.66) in the OP to 5.09 (95% CI, 3.40-6.78) in the ATP, demonstrating noninferiority and superiority of marstacimab (estimated ABR difference, -2.81 [95% CI, -5.42 to -0.20]; P = .0349). There were no deaths or thromboembolic events. Weekly subcutaneous marstacimab reduced ABR vs OD or RP therapy in the OP in individuals with severe HA or moderately severe to severe HB without inhibitors. Marstacimab was safe and well tolerated with no unanticipated side effects. This trial was registered at www.clinicaltrials.gov as #NCT03938792.

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Conflict of interest statement

Conflict-of-interest disclosure: C.K.L. has received honorarium from Amgen. D.M. has received research funding from Bayer, Pfizer, Novo Nordisk, Sanofi, Spark, Octapharma, and Roche; and has received honoraria from Bayer, Pfizer, Novo Nordisk, Sanofi, Sobi, and Octapharma. J.M. has received research funding from BioMarin, CSL Behring, Novo Nordisk, Pfizer, Roche, Sanofi, and Spark; is a member of scientific advisory committees for BioMarin, Novo Nordisk, Roche, Takeda, Regeneron, Sanofi, and Spark; and is a member of speakers bureaus for Novo Nordisk, Pfizer, Roche, Sanofi, and Takeda. O.B.Z. has received research funding from Sobi and Pfizer; and is a member of speakers bureaus for Sanofi, Takeda, Pfizer, Roche, Genveon, Novo Nordisk, and CSL Behring. R.Y. has received honoraria or speaker fees from Novo Nordisk, Pfizer, Sanofi, and Takeda. S.S.A. has received honoraria from Bayer and Pfizer. V.J.-Y. has received grants or contracts from F. Hoffmann-La Roche Ltd, Novo Nordisk, Sobi, Takeda, Grifols, Bayer, Pfizer, Octapharma, and CSL Behring; and has received consulting fees and payment or honoraria for lectures, presentations, speakers bureau, manuscript writing, or educational events from F. Hoffmann-La Roche Ltd, Novo Nordisk, Sanofi, Sobi, Takeda, Grifols, Bayer, Pfizer, Spark Therapeutics, BioMarin, Octapharma, and CSL Behring. Y.W. has received research grants from Pfizer, Novo Nordisk, and Novartis. Y.-S.P. reports research support from or participation as a principal investigator for Pfizer, BioMarin Pharmaceutical Inc, CSL Behring, Novo Nordisk, Sanofi, Takeda, and Chugai. A.P., C.T.T., S.R., and S.N. are employees and stockholders of Pfizer. E.H., R.M., and J.T. were employees and stockholders of Pfizer at the time the study was conducted. The remaining authors declare no competing financial interests.

A complete list of the members of the BASIS Investigators appears in the supplemental Appendix.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Screening, enrollment, dosing, and progression in the BASIS study. Screening for patients without inhibitors to enter the BASIS study, enrollment into the OP, entry into the ATP, dosing with marstacimab, and progression to the ongoing open-label extension study. ∗Number of participants before the phase 3 study primary completion date (data cutoff, 17 April 2023). mITT, modified intent to treat.
Figure 2.
Figure 2.
Results of primary and key secondary efficacy end points. The model-based ABR during the (A-B) OP and ATP for the primary end point (treated bleeds) and (C-D) key secondary end points in the OD group (A,C) and the RP group (B,D). Ratio estimate, 95% CI and P value are shown for marstacimab vs previous OD therapy; difference estimate and 95% CI are shown for marstacimab vs previous RP (P values not shown because comparisons did not reach significance). The analyses include participants who received ≥1 dose of marstacimab prophylaxis in the ATP. ABR was calculated for time on treatment in each phase. For participants who had a dose escalation, the duration on marstacimab 300 mg was not included. For the OD group, P values are for the null hypothesis that the ABR ratio (marstacimab prophylaxis to OD treatment) equals 0.5. For the RP group, P values are for the null hypothesis that the difference (marstacimab prophylaxis minus RP) equals 0.0. Hierarchical testing precluded superiority testing for the secondary end points in the RP group (panel B) because superiority was not demonstrated in the physical health domain of the Haem-A-QoL.
Figure 3.
Figure 3.
Key patient-reported outcomes for HRQoL. Nonparametric analysis of change from baseline to month 6 during the OP and from last day of the OP to month 6 of the ATP for the Haem-A-QoL (A), EQ-5D-5L (B), and EQ-VAS (C) measures. Estimated median difference (95% CI) of marstacimab vs previous OD therapy and RP. Missing values were imputed using multiple imputation methods based on missing at random assumption.
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