Factor VIIa marzeptacog alfa (activated)

Marzeptacog alfa (activated) is a potent, next-generation Factor VIIa that was created to allow for the effective, long-term, prophylaxis in individuals with hemophilia with inhibitors, acquired hemophilia and other bleeding disorders. It was designed to combine higher clot-generating activity and longer activity at the site of bleeding and therefore improved efficacy. Catalyst anticipates that marzeptacog alfa (activated) could be used for both subcutaneous prophylactic treatment and intravenous acute treatment. The Company initiated a Phase 2/3 subcutaneous prophylaxis efficacy trial in the first quarter of 2018.

Factor VIIa marzeptacog alfa (activated) Phase 2/3 efficacy trial - ongoing

The Phase 2 portion of the subcutaneous efficacy trial (NCT03407651) is an open-label study in individuals with hemophilia A or B with inhibitors. The objective of the trial is to eliminate, or minimize, spontaneous bleeding episodes by using individualized dose escalation, if a spontaneous bleeding event occurs. The primary endpoint will be a reduction in annualized bleed rate (ABR). Each individual’s recorded ABR will serve as the control. A secondary endpoint will compare the proportion of days with bleeding recorded during the prior 6 months with the proportion of any bleeding days during marzeptacog alfa (activated) (MarzAA) treatment. The trial will enroll up to 12 individuals with hemophilia across approximately 10 clinical trial sites globally. 

Five subjects have successfully completed long-term daily dosing with MarzAA. These five subjects had an ABR range of 15.2-26.7 before MarzAA treatment. Three participants experienced no bleeds with individualized dosing of either 30 µg/kg or 60 µg/kg MarzAA and two others had clinically significant reductions in ABR. The median proportion of days with bleeding during the pre-study period was 11.9% and this was significantly reduced to a median of 0.5% during the treatment period. Through a total of more than 300 days of subcutaneous dosing, no injection site reactions or anti-drug antibodies to MarzAA have been detected. In one subject, two subcutaneous injections resulted in a mild localized hematoma that resolved without sequelae or treatment. Final data from the study are expected in the first half of 2019.

Factor VIIa marzeptacog alfa (activated) efficacy trial design

MarzAA Phase 2 image

Factor VIIa marzeptacog alfa (activated) Phase 1 trial - completed

Marzeptacog alfa (activated) has successfully completed a Phase 1 intravenous clinical trial in individuals with severe hemophilia A and B with and without inhibitors. Positive results, showing favorable safety, tolerability and pharmacological data after single intravenous doses of marzeptacog alfa (activated), were originally reported from this open label, multicenter Phase 1 clinical trial at the International Society on Thrombosis and Haemostasis (ISTH) meeting in 2015 and were recently published in the Journal of Thrombosis and Hemostasis.

Marzeptacog alfa (activated) has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA) for routine prophylaxis to prevent bleeding episodes in individuals with hemophilia A or B with inhibitors.