Gene therapy ‘clearly superior’ for patients with hemophilia B
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Etranacogene dezaparvovec conferred superior bleed control for adults with moderate or severe hemophilia B compared with standard factor IX prophylaxis, according to results of the phase 3 HOPE-B study.
Findings from the trial’s primary analysis — published in The New England Journal of Medicine — showed a single dose of the gene therapy induced sustained factor IX activity in recipients, with no treatment-related adverse effects.
“This therapy is really changing people’s outlook toward the future,” Steven W. Pipe, MD, professor of pediatrics and pathology and medical director of the pediatric hemophilia and coagulation disorders program at University of Michigan, told Healio. “What we do right in medicine is relieve people from the burden of their condition, and I think this gene therapy is delivering on all fronts.”
Background
Etranacogene dezaparvovec (Hemgenix, CSL Behring) is an adeno-associated virus vector-based gene therapy that carries a gene for clotting factor IX and is given as a one-time IV infusion. The therapy causes the patient’s liver to produce factor IX protein, which increases factor IX levels in the blood and limits bleeding episodes.
The FDA approved etranacogene dezaparvovec in November for treatment of certain adults with hemophilia B based on results of the ongoing HOPE-B trial.
Durability has been a major concern for gene therapy, according to Pipe. At issue is whether factor IX expression can be maintained at normal or near-normal levels over the long term.
“Now we have phase 3 data showing stable levels out through 2 years,” he said. “We're expecting this to be a durable solution.”
Methodology
HOPE-B evaluated the safety and efficacy of gene therapy with etranacogene dezaparvovec compared with prophylactic factor IX replacement therapy among adults with moderate to severe hemophilia B.
The study included 54 men (mean age, 41.5 ± 15.8 years; range, 19–75; 74% white) with hemophilia B regardless of preexisting adeno-associated virus serotype 5 neutralizing antibodies.
Eighty-one percent of participants had severe hemophilia B at the time of diagnosis, and all reported actively receiving factor IX replacement therapy.
The trial design included a lead-in period of factor IX prophylaxis lasting at least 6 months, followed by infusion of etranacogene dezaparvovec at a dose of 2 × 1013 genome copies/kg.
Annualized bleeding rate — evaluated as part of a noninferiority analysis comparing the rate during the lead-in period with the rate during months 7 through 18 after infusion of etranacogene dezaparvovec — served as the study’s primary endpoint. Secondary endpoints included additional efficacy measurements and safety.
Key findings
Investigators reported a significant decrease in annualized bleeding rate, from 4.19 (95% CI, 3.22-5.45) during the lead-in period to 1.51 (95% CI, 0.81-2.82) during months 7 through 18 after treatment.
The observed annualized bleeding rate ratio of 0.36 (95% CI, 0.2-0.64) for the post-treatment period compared with the lead-in period demonstrated noninferiority and superiority of etranacogene dezaparvovec vs. factor IX prophylaxis, the researchers noted.
Participants exhibited significant increases in factor IX activity compared with baseline at both 6 months and 18 months after treatment. Conversely, the amount of factor IX concentrate study participants used decreased by a mean of 248,825 IU/year per participant after treatment.
Clinical implications
Gene therapy with etranacogene dezaparvovec is “clearly superior to routine factor IX prophylaxis” no matter how investigators measured it, Pipe said. That included improvement in annualized bleed rate, reducing spontaneous bleeds and reducing joint bleeding.
“We are excited to be able to deliver this clinically,” he told Healio. “We still have some hurdles with the payers to sort out ... but if you look at any cost-effectiveness analysis that's been conducted, gene therapy always comes out as the better option over almost any time span.”
For more information :
Steven W. Pipe, MD, can be reached at Departments of Pediatrics and Pathology, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-5718; email: ummdswp@med.umich.edu.
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