Marstacimab’s once-weekly subcutaneous administration demonstrated clinically meaningful superiority in key bleeding outcomes for adolescents and adults with hemophilia A or B.
The phase 3 BASIS study (NCT03938792), evaluating marstacimab (Hympavzi; Pfizer) in patients aged 12 to 74 years with hemophilia A or B and inhibitors, demonstrated marked improvements in bleeding outcomes compared with standard on-demand (OD) bypassing therapy.1
Treatment with marstacimab resulted in a statistically significant and clinically meaningful 93% reduction in the mean treated annualized bleeding rate (ABR). According to a press release, Pfizer presented the results at the American Society of Hematology Annual Meeting and Exposition in Orlando, Florida, over the weekend.
During the 12-month active treatment period in the BASIS trial, 48 individuals received a 300-mg loading dose of marstacimab followed by a once-weekly 150-mg subcutaneous dose. The reduction in treated ABR was substantial: 1.39 with marstacimab vs 19.78 during the preceding OD bypassing-agent phase, representing a 93% decrease and clear statistical and clinical superiority (1.39 [95% CI, 0.85-2.29] vs 19.78 [95% CI, 16.12-24.27]; P < .0001). Findings were consistent across hemophilia types, age groups, and global regions. Median ABR also fell to 0 during marstacimab prophylaxis compared with 16.42 during OD care (95% CI, 0.00-69.10).
"The emergence of inhibitors poses significant treatment challenges and can increase disease burden for people living with hemophilia A or B,” said Davide Matino, MD, MSc, principal investigator of the BASIS trial and associate professor of medicine at McMaster University in Hamilton, Ontario, Canada, in a statement.
"In patients with inhibitors, this study demonstrates [marstacimab]'s potential as a safe and efficacious treatment option that not only significantly reduced bleeding episodes via a once-weekly subcutaneous administration but also demonstrated improvement in certain aspects of health-related quality of life," said Matino.
Superiority extended across all secondary bleeding end points. Spontaneous bleeds, joint bleeds, target-joint bleeds, and total treated and untreated bleeds were all significantly reduced during treatment with marstacimab vs OD therapy. Beyond bleed reduction, early signs of improvement in health-related quality of life were observed at 6 months, including benefits in physical health measures, overall quality-of-life scores, and patient-reported mobility and pain-related domains.
Safety findings were consistent with what has been previously observed in the marstacimab program. No deaths or thromboembolic events were reported among the 51 patients in the safety population. Most adverse events were mild or moderate, and only one treatment-related serious adverse event led to discontinuation.
In October 2024, the
Approval was supported by earlier phase 3 data showing dramatic reductions in bleeding rates after transitioning from on-demand or prophylactic factor replacement to marstacimab prophylaxis. Reported adverse reactions included injection-site reactions, pruritus, and headache, aligning with the safety observations in the inhibitor cohort. The product also carries warnings regarding thrombotic risk, hypersensitivity, and embryofetal toxicity.
As phase 3 inhibitor data continue to mature, the expanding clinical profile of marstacimab may eventually position the therapy as a consistent prophylactic option across a broader spectrum of patients with hemophilia A or B, whether or not inhibitors are present.
Pfizer has submitted the inhibitor cohort data to the FDA and European Medicines Agency for regulatory review.
“It is encouraging that these data demonstrate the potential of Hympavzi to combine efficacy, safety, and straightforward administration for adults and adolescents living with hemophilia A or B with inhibitors and address a significant patient need,” said Michael Vincent, MD, PhD, chief inflammation and immunology officer at Pfizer, in the press release. "We look forward to potentially making this treatment available for these patients as Pfizer continues its ongoing effort spanning more than 40 years to improve hemophilia care.”
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