Hemgenix seen to reduce bleeds better in hemophilia B in new data
Approved uniQure gene therapy found superior to preventive treatment
Hemgenix (etranacogene dezaparvovec), the first gene therapy approved for adults with hemophilia B, has been shown to work better than standard preventive replacement therapy to lower the frequency of bleeds — both spontaneous and joint bleeds — in this patient population.
The therapy also was superior in sustainably increasing the activity of factor IX (FIX), the blood clotting protein missing in people with hemophilia B.
Additionally, and in line with previous reports, Hemgenix was found to be able to reduce or eliminate the need for standard preventive (prophylactic) FIX replacement therapies in hem B patients.
That’s all according to 18-month data from the Phase 3 HOPE-B trial (NCT03569891), recently published in the New England Journal of Medicine in the study, “Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B.”
“These results highlight the potential benefits of this novel gene therapy approach and further reinforce that those treated with Hemgenix in clinical trials have achieved durable factor IX activity levels and remained free of prophylactic factor IX replacement for years following a single administration,” Ricardo Dolmetsch, PhD, president of research and development at uniQure, the therapy’s original developer, said in a company press release.
New HOPE-B trial data show benefits of gene therapy
Findings from HOPE-B supported Hemgenix’s approvals in the U.S. and the European Union — with conditional approval in the EU granted just last month. The gene therapy also is approved in Iceland, Liechtenstein, and Norway, and is under regulatory review in the U.K.
“We at uniQure are incredibly pleased to have the clinical results from the global HOPE-B pivotal trial featured in such a prominent peer-reviewed journal,” Dolmetsch said. “uniQure is immensely proud to have led the multi-year clinical development program for Hemgenix that included the HOPE-B pivotal trial.”
Hemophilia B is caused by mutations in the F9 gene, which encodes the blood clotting protein FIX. Such mutations result in FIX deficiency and impair the blood clotting process. As a result, people with hem B can experience spontaneous bleeding episodes or prolonged bleeds after surgery or an injury.
Standard treatment for moderate to severe hemophilia B includes FIX replacement therapy — a form of treatment in which patients are given a lab-made version of FIX. However, patients must follow a lifelong regimen of regular injections. And despite their effectiveness, spontaneous bleeds, pain, and joint damage may still occur with replacement therapy.
Hemgenix, previously known as EtranaDez or AMT-061, carries FIX-Padua, a highly functional version of the F9 gene packaged within a modified and harmless adeno-associated virus (AAV5). Infused directly into the bloodstream (intravenously), the therapy targets liver cells, the body’s main producers of clotting factors, with the goal of restoring the production of functional FIX to prevent and control bleeds for long periods.
The ongoing, open-label HOPE-B trial enrolled 54 men, ages 18 and older, with moderate to severe hemophilia B. The study excluded participants with a history of neutralizing antibodies against FIX, called inhibitors, but included those with antibodies against the AAV5 delivery virus.
Before being given an infusion of Hemgenix, participants received at least six months of standard FIX replacement therapy during a lead-in period. The trial’s main goal was to evaluate changes in the annualized bleeding rate (ABR), or the number of bleeds patients experienced per year, between seven and 18 months, compared with the rate seen during the lead-in.
Favorable safety profile seen in men with hem B
As previously reported, data showed that the ABR for all bleeding episodes dropped from 4.19 during the lead-in period to 1.51 post-treatment, representing a reduction of 64%. Similarly, the ABR for spontaneous bleeds dropped by 71%, while that for joint bleeds decreased by 78% after 18 months, or 1.5 years.
For most participants (81%), FIX activity levels were less than 1% of normal at diagnosis. Three weeks after treatment with Hemgenix, FIX levels rose to 27%, then to 36% after six months, which was sustained at 34% through 18 months.
From three weeks to 18 months, 52 patients (96%) stopped FIX replacement therapy. The annualized FIX infusion rates fell from 72.5 per participant during the lead-in period to 2.5 infusions post-treatment.
Among patients with preexisting antibodies against AAV5, mean FIX activity was at 31% after 18 months compared with 40% in those without these antibodies.
“HOPE-B was also the first and only phase 3 study to demonstrate efficacy of a gene therapy for hemophilia B in individuals with circulating neutralizing antibodies that have the potential to interfere with the effects of treatment,” said Steven Pipe, MD, HOPE-B’s principal investigator and a professor of pediatrics and pathology at the University of Michigan.
“Results from HOPE-B suggest that Hemgenix may be effective in a broad range of hemophilia B patients, regardless of prior exposure to common adeno-associated viruses,” Pipe said.
The results … add to the established body of evidence demonstrating the long-term efficacy and safety of Hemgenix and confirm that this innovative new medicine not only restores blood clotting factor to near normal levels and significantly reduces factor use, but also that gene therapy may reduce the burden of care and improve quality of life for people living with this life-long condition.
Treatment-related adverse events were reported in 37 patients (69%). These included headaches, flu-like symptoms, elevated levels of liver enzymes signaling liver injury, fatigue, nausea, and joint pain.
“[Hemgenix] had a favorable safety and efficacy profile in men with severe or moderately severe hemophilia B, including those with preexisting AAV5 neutralizing antibodies,” the researchers wrote, adding that the therapy “was superior to factor IX prophylaxis in terms of the annualized bleeding rate and was associated with sustained increased factor IX activity to the mild to near-normal range, with associated durable hemostatic [bleeding cessation] improvement.”
“Our findings suggest that gene therapy may reduce the burden of care and improve quality of life in patients with hemophilia B,” they wrote.
HOPE-B is slated to wrap up in March 2025.
“The results published in NEJM add to the established body of evidence demonstrating the long-term efficacy and safety of Hemgenix and confirm that this innovative new medicine not only restores blood clotting factor to near normal levels and significantly reduces factor use, but also that gene therapy may reduce the burden of care and improve quality of life for people living with this life-long condition,” Pipe said.
HOPE-B findings reported late last year showed Hemgenix’s safety and efficacy has been sustained for at least two years.