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Clinical Trial
. 2023 Jan;200(2):240-248.
doi: 10.1111/bjh.18495. Epub 2022 Oct 11.

Long-term safety and efficacy of the anti-tissue factor pathway inhibitor marstacimab in participants with severe haemophilia: Phase II study results

Johnny Mahlangu  1 , Jose Luis Lamas  2 , Juan Cristobal Morales  2 , Daniel R Malan  3 , John Teeter  4 , Robert J Charnigo  4 , Eunhee Hwang  4 , Steven Arkin  5
Affiliations
Clinical Trial

Long-term safety and efficacy of the anti-tissue factor pathway inhibitor marstacimab in participants with severe haemophilia: Phase II study results

Johnny Mahlangu et al. Br J Haematol. 2023 Jan.

Abstract

Marstacimab, an investigational human monoclonal antibody targeting tissue factor pathway inhibitor, demonstrated safety and efficacy in preventing bleeding episodes in patients with haemophilia. This multicentre, open-label study investigated safety, tolerability, and efficacy of long-term weekly prophylactic marstacimab treatment in participants with severe haemophilia A and B, with or without inhibitors. Adult participants were enrolled from a previous phase Ib/II study or de novo and assigned to one of two subcutaneous (SC) marstacimab doses: once-weekly 300 mg or a 300-mg loading dose followed by once-weekly 150-mg doses, for up to 365 days. Study end-points included safety assessments and annualised bleeding rates (ABRs). Of 20 enrolled participants, 18 completed the study. Overall, 70% of participants had treatment-emergent adverse events, including injection site reactions, injection site haematoma, and haemarthrosis. No treatment-related serious adverse events or thrombotic events occurred. Across all dose cohorts, mean and median on-study ABRs ranged from 0 to 3.6 and 0 to 2.5 bleeding episodes/participant/year respectively, demonstrating comparable efficacy to that observed in the short-term parent study. No treatment-induced anti-drug antibodies were detected. Once-weekly SC marstacimab prophylaxis was well tolerated, with an acceptable safety profile, and maintained long-term efficacy up to 365 days. (Clinicaltrials.gov identifier, NCT03363321).

Keywords: antibodies, monoclonal; clinical study; drugs, investigational; haemophilia A; haemophilia B.

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Conflict of interest statement

Johnny Mahlangu has served as a consultant or on advisory boards for Baxalta, BioMarin, CSL Behring, Catalyst Biosciences, Novo Nordisk, Roche and Spark; served on speakers’ bureaus for Novo Nordisk, Pfizer, Roche, Sanofi, Springer, and Takeda; and received research grants from Baxalta, BioMarin, Catalyst Biosciences, CSL, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Spark, Roche, and uniQure. Jose Luis Lamas and Daniel R. Malan report no conflicts to disclose. Juan Cristobal Morales has served on speakers’ bureaus for Novo Nordisk and Roche; served on advisory boards for BioMarin and Novo Nordisk, and received fellowship support from Novo Nordisk, Roche, and Takeda. John Teeter, Robert J. Charnigo, Eunhee Hwang, and Steven Arkin are employees of Pfizer Inc. and may own stock/options in the company.

Figures

FIGURE 1
FIGURE 1
Participant marstacimab dose assignments. Participants from Cohorts 1 and 4 in the previous study continued to receive 300 mg weekly, and Cohorts 2 and 3 in the previous study received the lowest dose determined to be safe and effective (300‐mg loading dose followed by 150 mg SC weekly). Two participants were recruited de novo into the present study. Both were treated at the lowest effective dose level (300‐mg loading dose followed by 150 mg SC weekly). SC, subcutaneous; QW, once weekly
See this image and copyright information in PMC

References

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