Gene therapy Beqvez sustains gains in 6-year hemophilia B study
Single infusion helped clotting, reduced bleeding
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A single infusion of Beqvez (fidanacogene elaparvovec-dzkt), a now-discontinued gene therapy for hemophilia B, led to sustained production of factor IX (FIX) — the clotting protein missing in people with the condition — for up to six years, reducing bleeding episodes and eliminating the need for routine preventive infusions in most patients.
The findings are based on data from 14 men with severe or moderately severe hemophilia B who first received Beqvez in an open-label Phase 1/2a clinical trial (NCT02484092), and after one year of follow-up entered a long-term observational study (NCT03307980) that monitored therapy’s safety and effectiveness for up to five additional years.
Beyond clinical benefits, patients reported lasting improvements in quality of life. The therapy was also found to be safe and well tolerated throughout the six years.
“Overall, [Beqvez] exhibited a favorable safety profile, sustained efficacy, and improved [patient-reported outcomes] for up to 6 years,” the researchers wrote.
The study, “Safety, efficacy and patient-reported outcomes 6 years after fidanacogene elaparvovec in adults with hemophilia B,” was published in Blood Advances. It was funded by Pfizer, the company that marketed Beqvez.
Therapy discontinued due to limited interest
Hemophilia B is caused by mutations in the F9 gene leading to a deficiency of FIX. Without enough FIX, blood does not clot properly, leading to easy and frequent bleeding episodes. Repeated bleeding, especially into joints, can cause joint damage, chronic pain, and reduced mobility.
Standard treatment involves regular infusions of factor replacement therapies that provide the body with a functional version of the FIX protein to restore blood clotting and prevent bleeding episodes. However, such treatment can be time-consuming, costly, and burdensome for patients.
Beqvez is designed to deliver a highly functional version of the F9 gene to liver cells — where clotting proteins are mostly produced — restoring the body’s ability to produce functional FIX protein with a single intravenous (into-the-vein) infusion. The therapy was approved in the U.S. in 2024 as a treatment for certain adults with moderate to severe hemophilia B. However, Pfizer discontinued its development and commercialization in February last year, citing limited patient and physician uptake.
Earlier results from the Phase 1/2a study and its extension showed that a single infusion of Beqvez at a dose of 0.5 trillion vector genomes per kg (vg/kg) could safely increase FIX levels while reducing bleeding episodes and the need for routine factor replacement therapy. The newly reported data provide a complete picture of outcomes over six years, including long-term safety and effectiveness and changes in patients’ quality of life.
Most participants (71.4%) were age 35 or older when they received Beqvez. Of the 14 men who entered the long-term follow-up, 11 completed the full six years. Two withdrew during the study, and one was lost to follow-up.
Before the gene therapy, nearly two-thirds (64.3%) had FIX activity levels of less than 1% of normal, consistent with severe hemophilia B. The remaining 35.7% had FIX activity levels ranging from 1% to 2% of normal, indicating moderately severe disease.
Treatment led to sustained FIX production. After a single infusion, mean FIX activity levels among all participants rose to 24.7% at year 2, and to 26.1% at year six among the 11 participants with available data.
The sustained increase in FIX activity levels translated into fewer bleeding events. Before Beqvez, participants experienced a mean of 9.5 treated bleeding episodes per year. After treatment, the mean dropped to less than one treated bleed per year during the six-year follow-up.
Overall, 64.3% of participants experienced no bleeds after receiving Beqvez, and 71.4% had none during years 2 through 6. Target joint bleeding and/or symptoms — meaning bleeding or related problems that repeatedly affect the same joints — which affected 78.6% of participants before treatment, became rare at later follow-up visits.
None of the participants resumed routine preventive FIX infusions.
Participants also reported lasting improvements in daily life. Scores on a hemophilia-specific quality-of-life questionnaire improved as early as year 1 and remained higher than before treatment through year 6, with meaningful gains in overall well-being, physical health, and participation in sports and leisure activities.
Patients also reported better overall health and maintained or increased physical activity levels. Pain levels remained low and stable during follow-up.
The therapy appeared generally safe and well tolerated over the six years. Nine serious adverse events were reported in four participants, but none was deemed treatment-related. Temporary increases in liver enzymes occurred in eight participants, but these were generally mild and resolved without treatment.
Beqvez “exhibits a favorable safety profile, sustained efficacy with FIX activity in the mild hemophilia range for most participants, and improved [patient-reported outcomes] for up to 6 years,” the researchers wrote. They noted that despite the relatively small number of participants, the results provide the longest follow-up data available for this gene therapy in hemophilia B.
Continued follow-up in a longer-term extension trial (NCT05568719), which will monitor participants for up to 15 years after treatment, along with data from the ongoing Phase 3 BENEGENE-2 clinical trial (NCT03861273), will provide additional insight, the researchers wrote.
