Pfizer Reports Patient Death in Hympavzi Hemophilia Trial, Raises Safety Concerns

Pharmaceutical giant Pfizer has disclosed a patient death in a long-term follow-up clinical trial of its recently approved hemophilia therapy, Hympavzi. The incident has prompted a thorough investigation and raised questions about the drug's safety profile.

Patient Death and Trial Details

On December 14, 2025, a patient participating in an open-label extension study of Hympavzi (marstacimab) suffered a fatal thrombotic stroke following minor surgery. The patient, who had hemophilia A with active inhibitors, had been enrolled in the trial since 2022, transitioning from a Phase III study to the extension phase in 2023.

Pfizer reported that the patient was receiving Hympavzi as prophylaxis along with recombinant factor VIIa to prevent bleeding post-surgery. Prior to the fatal event, the patient experienced serious adverse events, including a stroke and bleeding in the brain.

Regulatory Status and Mechanism of Action

Hympavzi, an IgG1 monoclonal antibody, was approved by the U.S. Food and Drug Administration in October 2024 as a once-weekly subcutaneous prophylactic injection for hemophilia A or B patients aged 12 and older without inhibitors. The therapy subsequently gained authorization in Europe, the UK, and Switzerland.

The drug's mechanism of action involves targeting the Kunitz domain 2 of the tissue factor pathway inhibitor protein, enhancing coagulation in hemophilia patients. However, this mechanism also makes thrombosis an "adverse event of special interest," according to the World Federation of Hemophilia (WFH) and the National Bleeding Disorders Foundation (NBDF).

Investigation and Industry Response

Pfizer is currently working with the trial investigator and an independent data monitoring committee to gather more information about the incident. The company has emphasized its commitment to transparency and patient safety, stating that it has informed regulators and investigators of the death.

In a letter to the hemophilia community, Pfizer noted that it is considering co-existing medical conditions and concomitant medications in its investigation. The company maintains that based on current knowledge and overall clinical data, it does not anticipate any impact on the safety of approved Hympavzi use.

The WFH and NBDF have acknowledged the incident, reminding the community that Hympavzi is not currently approved for treating hemophilia with inhibitors. They also noted that thrombotic events have been recorded with other non-factor hemophilia therapies.

As the pharmaceutical industry closely monitors this development, patients currently taking Hympavzi are advised to continue treatment as directed by their healthcare providers while awaiting further information from the ongoing investigation.