Favorable results reported for Hympavzi for those with inhibitors | ASH 2025

The FDA approved Hympavzi (marstacimab), a once-weekly nonfactor replacement therapy for people with hemophilia A and B, last year. But the approval was limited to people that haven’t developed inhibitors, antibodies that attack the blood clotting factors that people with hemophilia are treated with because their own blood lacks them. People with hemophilia A lack factor VIII, and those with hemophilia B lack factor IX. Approximately 20% to 30% of people with severe cases of hemophilia A develop the inhibitors, and approximately 1.5% to 3% of those with severe hemophilia B do.

Now there is evidence that Hympavzi is also effective for people with hemophilia A and B who have developed inhibitors, a development that could lead the FDA to broaden the treatment’s approval to the patient population with inhibitors.

Results of an open-label, single-arm study presented at the annual meeting of the American Society of Hematology (ASH) earlier this month showed that Hympavzi greatly reduced bleeds compared with “bypassing agents,” clotting agents that people with hemophilia with inhibitors are treated with instead of factor therapy that the inhibitors render ineffective. The results also showed improved quality of life, as measured by standardized questionnaires. The investigators, led by Davide Matino, M.D., M.Sc., an associate professor of medicine at McMaster University in Hamilton, Ontario, Canada, reported that while 3 in 4 patients reported adverse events, most of the events were mild or moderate, with the most common being COVID-19 infection.

“The emergence of inhibitors poses a significant treatment challenges and can increase disease burden for people living with hemophilia A or B,” Matino said in a news release about the trial results from Pfizer, the manufacturer of Hympavzi.

Matino also noted the improvement in health-related quality of life. “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 once-weekly subcutaneous administration but also demonstrated improvement in certain aspects of health-related quality of life.”

Hympavzi is one of the new generation of “rebalancing” treatments of hemophilia A and B that improve blood clotting by damping anticoagulation activity rather than boosting clotting activity. The other FDA-approved rebalancing agents are Alhemo (concizumab) and Qfitlia (fitusiran).

The positive results from the phase 3 BASIS study of patients with hemophilia A and B without inhibitors have been previously published. The part of the BASIS study assessing patients with inhibitors enrolled 60 patients, 40 of whom had hemophilia A and 13 of whom had hemophilia B. The median age was 23, and most of the patients were Asian individuals (53.3%) or White individuals (31.7%). The study had two phases: an initial observation phase of six months during which the study participants were treated with bypassing agents, followed by a “yearlong active treatment” phase during which they were treated with weekly subcutaneous injections of Hympavzi. The vast majority — 57 of 60 — of the patients in the observation phase were treated on an on-demand basis, which means they were treated to stop a bleed rather than regularly on a prophylactic basis.

The main comparison delineated in the results presented at the ASH meeting was between the experience the study participants had during the six-month observational phase and the experience they had on active treatment with Hympavzi. Because the majority of the patients in the observational phase were treated on an on-demand basis, the comparison was principally between on-demand treatment with a bypassing agent and treatment with Hympavzi.

Matino and his colleagues reported in the abstract that Hympavzi (they used the generic name in the abstract) reduced the annualized bleed rate for treated bleeds from 19.78 during the observational period to 1.39 during active treatment. Furthermore, the average annualized bleed rates for a number of the different categories of bleeds experienced by people with hemophilia A and B were much lower during active treatment with Hympavzi than with on-demand treatment during the observational phase (joint bleeds, 1.10 vs. 15.5; spontaneous bleeds, 0.87 vs. 15.27; target joint, 0.79 vs. 6.42; and total bleeds [treated and untreated], 4.36 vs. 27.79).

A variety of measures of health-related quality of life also pointed to the superiority of treatment with Hympavzi over on-demand treatment with a bypassing agent, with the exception of the EuroQol Visual Analogue Scale.

In addition to COVID-19, the adverse events experienced during treatment with Hympavzi included upper respiratory tract infections (15.7%), fibrin D-dimer increases (9.8%) and headache (9.8%) according to the abstract. One patient reported a treatment-related skin rash (grade 3) that was classified as a serious adverse event during active treatment with Hympavzi that led to study discontinuation, and 10 patients temporarily discontinued or reduced their dose of Hympavzi due to an adverse event, with COVID-19 infection the most common event (seven of the patients). Antidrug antibodies were detected in 10 of 51 patients, but the titers were low, and nine of the 10 cases resolved by the end of the study, reported Matino and his colleagues. No deaths or thrombotic events were reported, according to their abstract.