Hympavzi Recommended for Approval in Europe for Severe Hemophilia A, B

The European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) recommended the granting of marketing authorization for Hympavzi (marstacimab) for treating bleeding episodes in people aged 12 years or older with severe hemophilia A and B. The drug is now pending a final decision from the European Commission. 

The EMA granted Hympavzi orphan status for treating hemophilia B in December 2src23. The EMA will now review available information to determine whether this status can be maintained. The orphan designation is given to drugs intended for use with rare diseases. These drugs must fulfill certain criteria in order to benefit from such incentives as protection from competition. 

Hemophilia A and B are rare bleeding disorders caused by genetic mutations that lead to a lack of or complete absence of coagulation factor VIII or factor IX. 

The main symptom of hemophilia is bleeding that does not stop. The condition may manifest as skin that bruises easily, long-lasting bleeding from wounds, and pain and stiffness around joints due to internal bleeding. Around 8srcsrc,srcsrcsrc people worldwide are predicted to be affected by hemophilia. 

The active substance of Hympavzi is marstacimab, a human monoclonal antibody that inhibits anticoagulation activity of tissue factor pathway inhibitor. In doing so, it increases the availability of free factor Xa, which in turn increases thrombin generation and promotes hemostasis. 

Phase 3 Clinical Trial 

The CHMP’s recommendations come after results from a phase 3 clinical trial called BASIS, which evaluated Hympavzi’s efficiency in treating 116 male participants aged between 12 and 75 years of age with severe hemophilia A or moderate to severe hemophilia B. 

Participants received marstacimab during a 12-month active treatment period vs standard care involving routine prophylaxis and an on-demand intravenous regimen with factor VIII or factor IX over a 6-month observational period. 

Primary endpoints were the annualized bleeding rate (ABR) for treated bleeding events and safety outcomes. The ABR was calculated as the number of reported bleeding events divided by the number of months in the reporting timeframe, which was then multiplied by 12. 

Secondary endpoints included the incidence of various types of breakthrough bleeds and measures of health-related quality of life. 

Compared with routine prophylaxis, treatment with marstacimab resulted in a 35% mean reduction in ABR over 12 months. Compared with on-demand treatment, the drug reduced the ABR by 92%.

After 12 months of treatment, patients had the option to continue the marstacimab regimen as part of a long-term extension study. For up to 16 months, participants experienced consistent reductions in ABR compared with on-demand treatment, and further reductions compared with routine prophylaxis. 

In terms of secondary endpoints, marstacimab demonstrated superiority in bleeding-related measures compared with on-demand treatment, and noninferiority compared with routine prophylaxis. The drug also showed nonsignificant improvements in health-related quality of life measures compared with on-demand treatment and noninferiority compared to routine prophylaxis. 

Hympavzi was generally well tolerated and was observed to have a safety profile consistent with that seen in previous phase 1 and 2 trials. The most common adverse events included COVID-19, hemorrhages, hepatic disorders, injection site reactions, hypersensitivity, and hypertension. 

No deaths occurred during treatment, although there was one treatment-related serious adverse event of peripheral swelling, and one patient discontinued the study owing to a non–treatment-related severe adverse event. 

Hympavzi will be available as a 15src-mg solution for injection. It is indicated for patients aged 12 years or older and weighing at least 35 kg with either severe hemophilia A without factor VIII inhibitors or severe hemophilia B without factor IX inhibitors. 

Treatment should begin in a nonbleeding state and should be prescribed and supervised by physicians experienced in treating hemophilia. 

Detailed recommendations for using the drug will appear in the summary of product characteristics, which will be published in the European Public Assessment Report and made available in all official European languages.

Annie Lennon is a medical journalist. Her writing appears on Medscape, Medical News Today, and Psych Central, among other outlets.