Pfizer has announced Phase 3 data demonstrating that its investigational therapy, HYMPAVZI (marstacimab), delivers significant reductions in bleeding episodes in adults and adolescents living with hemophilia A or B who have developed inhibitors.
Inhibitors are one of the most challenging complications of the disease.
The findings, released in an oral presentation at the 67th American Society of Hematology (ASH) Annual Meeting in Orlando and published simultaneously in Blood, show that HYMPAVZI achieved superiority across all key bleeding outcomes compared with standard on-demand treatment with bypassing agents. The therapy is administered as a once-weekly subcutaneous injection, a simpler alternative to current intravenous regimens and one that requires no treatment-related laboratory monitoring.
Inhibitors are antibodies that neutralise clotting factor therapies, representing a significant therapeutic barrier for thousands of people worldwide. Although hemophilia affects more than 800,000 people globally, about 20 per cent of those with hemophilia A and 3 per cent with hemophilia B eventually develop inhibitors that prevent factor replacement therapies from working.
“The emergence of inhibitors poses significant treatment challenges and can increase disease burden for people living with hemophilia A or B,” said Dr Davide Matino, BASIS Principal Investigator and Associate Professor of Medicine at McMaster University. “In patients with inhibitors, this study demonstrates HYMPAVZI’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.”
The BASIS Phase 3 study followed 48 adolescents and adults with severe hemophilia A or B with inhibitors. After a six-month observational period in which participants received their usual on-demand bypassing therapy, patients moved into a 12-month active treatment phase with HYMPAVZI.
The results include a 93 per cent reduction in mean treated annualised bleeding rate (ABR), consistent benefit across haemophilia type, age groups, and geographic regions, and superiority across all secondary endpoints, including spontaneous, joint, target-joint, and total bleeds
Patients also reported meaningful improvements in physical health and overall quality of life, including better mobility, less pain, and fewer limitations in daily activities.
HYMPAVZI was generally well tolerated, with no deaths or thromboembolic events observed in the 51-patient safety population. Most adverse events were mild or moderate, and only one treatment-related serious adverse event, skin rash, led to discontinuation.
“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 Dr Michael Vincent, Chief Inflammation and Immunology Officer at Pfizer. “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.”
Unlike conventional therapies that replace missing clotting factors, HYMPAVZI targets tissue factor pathway inhibitor, a natural brake on the body’s clotting process. By binding the Kunitz 2 domain of TFPI, the therapy aims to restore balance between clot formation and bleeding, offering durable protection through convenient once-weekly dosing.
HYMPAVZI is already approved in more than 40 countries, including Australia, for certain haemophilia patients without inhibitors. Pfizer has applied for HYMPAVZI to be funded via the National Blood Authority, with an application to the Medical Services Advisory Committee for inclusion on the National Products List currently under consideration.