Efficacy and safety of etranacogene dezaparvovec gene therapy for haemophilia B

A recent study showed that in patients with severe or moderately severe haemophilia B etranacogene dezaparvovec is an effective and safe therapeutic option that provides durable disease correction for a period of 24 months.  This study’s findings were published in the journal, Lancet Haematology. 
In the HOPE-B trial, a single-arm, multicentre, phase 3 trial, participants were administered a single infusion of etranacogene dezaparvovec (2 × 1013 genome copies per kilograms of bodyweight). The primary endpoint was the non-inferiority of the annualised bleeding rate (ABR) during the fifty two weeks following stable factor IX expression (defined as months seven-eighteen after treatment) compared to a lead-in period of at least six months where participants received their usual continuous factor IX prophylaxis. Additional post-hoc efficacy analyses, such as adjusted ABR, participants within factor IX ranges, factor IX activity, and factor IX use, along with safety analyses, were carried out at the 24-month mark after gene therapy. The data were analyzed in the full analysis set, which consisted of the 54 patients who received at least a partial dose of gene therapy.
The patients were followed for a median duration of 26.51 months (IQR 24.54-27.99), following a lead-in period of 7.13 months (6.51-7.82). In the updated analysis, comparing 7-24 months after gene therapy to the lead-in period, the mean adjusted ABR significantly decreased from 3.65 to 0.99 for factor IX-treated bleeds and from 4.18 to 1.51 for all bleeds. Throughout each 6-month interval after gene therapy, at least 67% of participants experienced no bleeding (36 out of 54 during months 0-6 and remained stable thereafter), in contrast to 14 (26%) out of 54 during the lead-in period. At the 24-month mark after gene therapy, only 1 (2%) participant had one-stage factor IX activity below 5%, while 18 (33%) had factor IX activity exceeding 40% (non-hemophilia range), with a mean factor IX activity that remained stable and sustained at 36.7% (SD 19.0%). At month 24 month, 52 individuals out of the total 54 participants (96%) exhibited endogenous factor IX remaining free of factor IX prophylaxis. No new safety concerns were identified, and there were no treatment-related serious adverse events or treatment-related deaths.
The above results demonstrated that etranacogene dezaparvovec is an effective and safe therapeutic choice for individuals suffering from severe or moderately severe haemophilia B, offering long-lasting disease correction over a span of 24 months.