Gene Therapy Superior to Factor IX Replacement for Hemophilia B

Etranacogene dezaparvovec gene therapy for hemophilia B was superior to prophylactic factor IX for decreasing annualized bleeding rate in a phase 3 clinical trial, researchers reported in The New England Journal of Medicine.

“Moderate-to-severe hemophilia B is treated with lifelong, continuous coagulation factor IX replacement to prevent bleeding,” the study authors explained in the study background. “Gene therapy for hemophilia B aims to establish sustained factor IX activity, thereby protecting against bleeding without burdensome factor IX replacement.

The open-label study included 54 men with hemophilia B. Participants underwent a lead-in period of at least 6 months, during which they received factor IX prophylaxis, followed by a single infusion of etranacogene dezaparvovec.

The rate of annualized bleeding decreased from 4.19 during the lead-in period to 1.51 during months 7 through 18 after etranacogene dezaparvovec treatment, according to the study. With a rate ratio of 0.36, etranacogene dezaparvovec demonstrated not only noninferiority but also superiority compared with factor IX prophylaxis.

“Factor IX activity had increased from baseline by a least-squares mean of 36.2 percentage points (95% CI, 31.4 to 41.0) at 6 months and 34.3 percentage points (95% CI, 29.5 to 39.1) at 18 months after treatment,” researchers reported, “and usage of factor IX concentrate decreased by a mean of 248,825 IU per year per participant in the post-treatment period (P < .001 for all three comparisons).”

Additionally, the study found the gene therapy to be safe and beneficial in patients with predose adeno-associated virus 5 neutralizing antibody titers of less than 700. There were no serious adverse events related to treatment.

Reference:
Pipe SW, Leebeek FWG, Recht M, et al. Gene therapy with etranacogene dezaparvovec for hemophilia B. N Engl J Med. 2023;388(8):706-718. doi:10.1056/NEJMoa2211644