New data suggest gene therapy may reach more hemophilia B patients
Study shows fewer bleeds and steady clotting levels years after treatment
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Hemgenix gene therapy for hemophilia B helped many patients, even those with pre-existing anti-AAV5 antibodies.
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It increased factor IX levels, significantly reduced bleeding, and lowered the need for routine infusions.
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Side effects were mostly mild or moderate, including temporary liver enzyme increases, with no long-term liver injury reported.
A single infusion of Hemgenix (etranacogene dezaparvovec-drlb) helped boost levels of factor IX (FIX), the clotting protein missing in hemophilia B, in many patients who already had antibodies against the viral carrier, according to new trial data.
The findings suggest the gene therapy may benefit a broader group of people than previously thought. These data come from an analysis of HOPE-B (NCT03569891), an open-label Phase 3 clinical trial that supported the approval of Hemgenix as the first gene therapy for hemophilia B, a rare genetic bleeding disorder caused by mutations in the F9 gene.
The results were detailed in the study, “Etranacogene dezaparvovec in hemophilia B participants with pre-existing AAV5 neutralizing antibodies: 4-year subgroup results from the HOPE-B trial,” published in Research and Practice in Thrombosis and Haemostasis. The study was funded by CSL Behring, the company that markets Hemgenix globally.
How Hemgenix works and why antibodies matter
Hemgenix uses an adeno-associated virus type 5 (AAV5) as a vector — a harmless virus used to deliver a working copy of a gene to liver cells, allowing the body to produce its own FIX. Some people naturally have antibodies against AAV5, which has previously limited who could receive gene therapy.
The goal of this analysis was to determine whether Hemgenix remained effective and well tolerated in patients who tested positive for anti-AAV5 antibodies. Before receiving the one-time infusion, all participants completed at least six months of standard preventive treatment with regular FIX infusions. Eligible participants had moderate-to-severe hemophilia B.
Of 54 participants, 21 had detectable anti-AAV5 antibodies on the day of treatment. Most had low to moderate antibody levels, while one had a very high level. After gene therapy, most participants produced stable levels of their own FIX. Average FIX activity was 36 International Units per deciliter (IU/dL) after one year and remained similar (34 IU/dL) after four years. According to the researchers, these levels were associated with reduced bleeding and were similar to values seen in the overall HOPE-B study population.
Two people were considered non-responders, meaning their FIX levels remained very low (at or below 2 IU/dL), and they continued preventive treatment. One received only about 10% of the planned dose due to an infusion-related reaction. The other had the highest antibody level measured at the time of treatment.
The yearly bleeding rate fell by about 74% overall. Spontaneous bleeds dropped by 79%, and joint bleeds by 82%. By the fourth year, none of the participants experienced spontaneous bleeds.
Use of standard FIX infusions fell by about 90% after treatment. Most participants stopped routine preventive infusions altogether. Only a small number continued or returned to regular FIX infusions, largely reflecting limited or lost response to the gene therapy.
Side effects were mostly mild and short-lived
All participants reported at least one side effect, but most were mild or moderate and occurred within the first three months after treatment. The most common were infusion-related reactions, such as allergic-like symptoms, and temporary increases in liver enzyme levels.
Liver enzyme increases, measured by levels of alanine aminotransferase (ALT), are a marker doctors monitor for possible liver inflammation. These increases were short-lived and treated with corticosteroids. Researchers reported no signs of late or long-term liver injury. A small number of serious side effects were reported, but detailed genetic analyses found no link to the gene therapy or viral vector.
Overall, the findings suggest the gene therapy provided lasting benefits for people with pre-existing anti-AAV5 antibodies, as long as their antibody levels were not very high. Production of FIX was sustained for years, bleeding was reduced, and most participants no longer needed routine preventive infusions. According to the researchers, these results could expand the number of patients who may benefit from gene therapy.
