After 4 years, hemophilia B bleeding rates remain low with Hemgenix
Gene therapy is being tested in Phase 3 HOPE-B clinical trial
Four years after treatment with the gene therapy Hemgenix (etranacogene dezaparvovec), most people with hemophilia B aren’t taking preventive therapies and annual bleeding rates remain substantially reduced, new data from the Phase 3 HOPE-B trial shows.
CSL Behring, which markets Hemgenix, presented the results at the 18th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) this month in Milan.
“These data continue to instill confidence in the clinical benefits of Hemgenix, highlighting the remarkable impact of this one-time treatment to reduce the frequency of bleeds in people with hemophilia B and improve quality of life by alleviating the burden of ongoing factor IX prophylactic treatment,” Andres Brainsky, vice president of research and development for hematology at CSL, said in a company press release.
Hemophilia B is caused by mutations in the gene that provides instructions for making the clotting protein factor IX (FIX). The absence of FIX, or its dysfunctioon leaves patients vulnerable to unusually frequent and prolonged bleeding episodes. Standard preventive, or prophylactic, treatment for hemophilia B consists of replacement therapies, which must be administered regularly to provide patients with a functional version of FIX and reduce the risk of bleeds.
Testing Hemgenix
Hemgenix delivers a working version of the gene that encodes FIX to cells in the liver, where most clotting factors are made. The goal is to restore the body’s ability to produce FIX on its own, reducing the risk of bleeds while decreasing or potentially eliminating the need for regular replacement therapy.
Hemgenix was approved in the U.S. in late 2022 for adults with hemophilia B who are on prophylaxis, or have or have had life-threatening bleeding or repeated, serious spontaneous bleeding episodes. The gene therapy has also been approved in the European Union, Australia, Canada, Switzerland, and the U.K.
These approvals were based mainly on findings from the Phase 3 HOPE-B trial (NCT03569891) wherein 54 men with severe or moderately severe hemophilia B were given a single infusion into a vein. Before receiving the gene therapy, all the men were treated with standard prophylaxis for at at least six months to establish a baseline for comparison.
Before treatment, all the men had FIX activity lower than 2% of normal and had more than four bleeds per year.
Top-line results from the study, which covered about 1.5 years of follow-up, showed Hemgenix safely increased FIX activity and reduced bleeding rates. These effects were sustained into two and three years of follow-up. The new data cover four years for 51 patients.
“CSL is committed to continuing to provide ongoing data analyses of Hemgenix, ensuring that healthcare providers and patients have the necessary information to make informed decisions about treatment options,” Brainsky said.
After four years of Hemgenix treatment
At four years post-treatment, the mean FIX activity was at 37.4%. For context, clotting factor activity levels between 5% and 40% are generally considered to be in the mild hemophilia range, while 50% or higher are considered to be within the normal range for people who don’t have hemophilia. The vast majority (94%) of patients treated with Hemgenix have remained off prophylactic replacement therapy for four years after treatment.
Consistent with the sustained increase in FIX activity, bleeding rates have remained low. As of year four, the mean adjusted annualized bleeding rate was 0.4 bleeds per year, which corresponds to a 90% decrease over before treatment rates. Joint bleeds were also lower, from a mean of 2.34 per year during prophylaxis to less than 0.1 per year in the fourth year after Hemgenix treatment.
“The four-year data from the HOPE-B study showed that a one-time infusion of Hemgenix (etranacogene dezaparvovec-drlb) continues to offer long-term durability, safety, and greater bleed protection versus prophylactic treatment in people living with hemophilia B,” said Steven Pipe, MD, a professor at the University of Michigan who presented the four-year data from HOPE-B, in an email to Hemophilia News Today. “Importantly, no patients returned to continuous prophylaxis treatment between years three and four after infusion, and 94% remained free of continuous prophylactic treatment four years after treatment with Hemgenix.”
No serious safety issues related to Hemgenix have been reported in the trial. Almost all side effects related to the therapy occurred within the first few months after treatment. The most common side effects reported were elevations in liver enzymes.
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