Hemgenix Gene Therapy’s Benefits Sustained for 2 Years in Phase 3 Trial

HOPE-B data supported therapy's recent US approval for hemophilia B

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The positive safety and efficacy profile of Hemgenix (etranacogene dezaparvovec) — the first and only approved gene therapy for adults with hemophilia B — was sustained for two years, according to data from a Phase 3 trial, CSL Behring has announced.

Findings were generally similar to previous trial analyses, which found the treatment to be safe, with an ability to lower bleeding rates, and enable patients to cease using preventive factor replacement therapies. Hemgenix also boosted the levels of factor IX (FIX) — the blood clotting protein that is missing in hemophilia B.

These findings from the pivotal HOPE-B trial (NCT03569891) supported the U.S. Food and Drug Administration’s recent approval of the therapy for adult hemophilia B patients who are currently on preventive treatment or have had life-threatening bleeding, or repeated and spontaneous bleeding episodes.

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Trial results support ‘potential long-lasting efficacy and safety of Hemgenix’

Results from the two-year analysis were discussed in a poster presentation at the 64th American Society of Hematology (ASH) Annual Meeting, held Dec. 10–13, in New Orleans. The poster was titled “Adults with Severe or Moderately Severe Hemophilia B Receiving Etranacogene Dezaparvovec in the HOPE-B Phase 3 Clinical Trial Continue to Experience a Stable Increase in Mean Factor IX Activity Levels and Durable Hemostatic Protection after 24 Months’ Follow-up.”

“The results presented at ASH continue to support the potential long-lasting efficacy and safety of Hemgenix and the ongoing benefit of this treatment for people living with hemophilia B,” Brahm Goldstein, MD, vice president of research and development, hematology, at CSL, which markets the therapy, said in a press release.

Goldstein added that Hemgenix “offers eligible people living with hemophilia B more choice in treatments and underscores CSL’s promise to deliver disruptive innovations, like gene therapy, that have the potential to improve the lives of people living with rare and serious diseases.”

The FIX deficiency that marks hemophilia B is caused by mutations in the F9 gene, which provides instructions for making FIX.

Previously known as EtranaDez or AMT-061, Hemgenix works by delivering a highly functional copy of F9 to liver cells, stimulating the production of FIX. Delivered as a one-time infusion directly into the bloodstream, the gene therapy is packaged into a modified viral carrier, called AAV5, which helps liver cells take up the treatment.

Gene therapy has great potential for rare bleeding disorders, and these results demonstrate long-lasting increases in factor IX activity levels, reaching levels near the normal range seen in people without hemophilia B

HOPE-B trial enrolled 54 adult men with moderate to severe hemophilia B

The ongoing HOPE-B trial enrolled 54 men, ages 18–75, with moderate to severe hemophilia B, with the goal of evaluating the treatment’s safety and efficacy over the course of five years.

The trial’s main goal was to achieve superior bleed control in the year after achieving stable FIX levels — months seven to 18 after the infusion — compared with bleed rates seen during a six-month lead-in period when patients were using standard of care FIX replacement therapy.

As previously described, this main goal was met, with annualized bleeding rates dropping by 64% seven to 18 months after infusion compared with the lead-in period. Moreover, FIX activity levels were significantly increased to about 37% of normal levels.

Two-year findings were largely similar, demonstrating a consistent and sustained effect of the gene therapy. FIX levels were maintained at about 37% of normal, and annualized bleeding rates were reduced by 64% during months 7–24 compared with the lead-in period.

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94% of participants eventually stopped using preventive FIX therapy

Overall, FIX therapy was reduced by 96% from the lead-in period to months 19–24, decreasing from a mean of 257,339 international units (IUs) per year, per participant, to 9,751 yearly IUs per patient.

All but three men (94%) were able to stop using preventive FIX therapy altogether up to 24 months.

“Gene therapy has great potential for rare bleeding disorders, and these results demonstrate long-lasting increases in factor IX activity levels, reaching levels near the normal range seen in people without hemophilia B,” said Steven Pipe, MD, principal investigator of HOPE-B.

“These data reinforce that people with hemophilia B who have received Hemgenix would likely achieve durable factor IX activity levels for years following a one-time infusion,” added Pipe, who is also a professor of pediatrics and pathology, and pediatric medical director of the hemophilia and coagulation disorders program at the University of Michigan.

Of the 557 adverse events reported, most (76%) were considered mild, 21% moderate, and 3% severe. A total of 93 side effects in 38 participants were considered treatment-related, none of which were deemed serious, and one of which occurred during months 18–24.

HOPE-B is expected to conclude in March 2025.

CSL Behring, which bought global rights to market Hemgenix from its developer, uniQure, says it plans to make the gene therapy available to patients as soon as possible. The therapy is also under regulatory review in Europe.