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uniQure announces positive top-line data from the HOPE-B pivotal trial of etranacogene dezaparvovec gene therapy in patients with hemophilia B.
uniQure N.V. announced positive top-line data from its pivotal, Phase III HOPE-B gene therapy trial of etranacogene dezaparvovec, an investigational adeno-associated virus five (AAV5)-based gene therapy for the treatment of patients with severe and moderately severe hemophilia B . This is the first data set to be reported from a Phase III gene therapy study in hemophilia B and, with 54 patients, the largest set of patients receiving a single gene therapy investigational product to be reported to date.
These clinical data were published as a late-breaking abstract, one of only six accepted for presentation at the 62nd Annual Meeting of the American Society of Hematology (ASH) and will be featured as an oral presentation in the conference on December 8, 2020.
The pivotal, Phase III HOPE-B clinical trial of etranacogene dezaparvovec is an open-label, single-dose, single-arm, multi-national trial in adult males with severe or moderately severe hemophilia. All patients required prophylactic routine FIX replacement prior to entering the clinical trial, and patients were not excluded from the trial based on pre-existing neutralizing antibodies (NAbs) to AAV5.
Patients in the HOPE-B clinical study were initially enrolled into a prospective, observational lead-in period of at least six months during which bleeding events and FIX replacement therapy usage were monitored. Fifty-four patients received a single intravenous infusion of etranacogene dezaparvovec gene therapy at 2x1013 gc/kg, including 23 patients who had pre-existing NAbs to AAV5. Patients are then evaluated to assess FIX activity determined by a one-stage assay performed at a central laboratory, annualized bleeding rates and usage of Factor IX replacement therapy. Patients will be monitored for five years to evaluate the safety of etranacogene dezaparvovec.
HOPE-B Primary Endpoint of FIX activity at 26 weeks :FIX activity in the 54 patients increased rapidly after dosing from less than 2% to a mean of 37.2 percent at 26 weeks, meeting the first primary endpoint. No correlation between pre-existing NAbs and FIX activity was found in patients with NAb titers up to 678.2, a range expected to include more than 95% of the general population; one patient with a NAb titer of 3,212.3 did not show an increase in FIX activity.
During the 26-week period after dosing, 72 percent of patients (39/54) reported no bleeding events. Fifteen patients reported a total of 21 bleeds. Mean annualized usage of FIX replacement therapy, a secondary endpoint in the clinical trial, declined by 96 percent. Etranacogene dezaparvovec was generally well-tolerated with no treatment-related serious adverse events. Most adverse events were classified as mild (81.5 percent). Most common events included transaminase elevation treated with steroids per protocol (9 pts; 17%), infusion-related reactions (7 pts; 13%), headache (7 pts; 13%) and influenza-like symptoms (7 pts; 13%). Liver enzyme elevations resolved with a tapering course of corticosteroids and FIX activity remained in the mild range in the steroid treated patients. No relationship between safety and NAbs titers was observed.
Condition: Haemophilia B
Type: drug