uniQure (QURE) Announces Positive 52-Week Clinical Data from HOPE-B Pivotal Trial of Etranacogene Dezaparvovec Gene Therapy in Patients with Hemophilia B and Provides Regulatory Update

uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced positive 52-week clinical data on all patients 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. These are the first clinical data to be reported from a Phase III gene therapy study in hemophilia B and, with 54 patients, the largest set of hemophilia B patients receiving a single gene therapy investigational product to date.

Data from the HOPE-B pivotal study showed that participants continued to demonstrate durable, sustained increases in Factor IX (FIX) activity at 52-weeks post-infusion with a mean FIX activity of 41.5 percent of normal, as measured by a one-stage APTT-based clotting assay, compared to a mean FIX activity of 39.0 percent of normal at 26-weeks of follow-up. There continued to be no clinically significant correlation between pre-existing neutralizing antibodies to AAV5 (NAbs) and FIX activity in patients with NAb titers up to 678.2, a range expected to include more than 93 percent of the general population.

During the 52-week period, a single dose of etranacogene dezaparvovec significantly reduced the annualized rate of bleeding requiring treatment by 80 percent from a prospectively collected 3.39 at baseline to 0.68 bleeding episodes per year (p-value <0.0001). The annualized rate of spontaneous bleeding requiring treatment was also significantly reduced by 85 percent from a prospectively collected 1.16 at baseline to 0.18 bleeds per year during the 52-week period (p-value <0.0001).

Usage of FIX replacement therapy (IU/year and infusions/year) in all patients declined 96 percent during the 52-week period, with 52 of 54 patients (96 percent) successfully discontinuing their prophylactic infusions. As previously announced, of the two non-responders, one patient only received a partial dose (less than 10 percent of the dosage) due to an infusion reaction and a second patient had an unusually high pre-existing NAb titer of 3,212, which is expected in less than 1 percent of the general population.

Etranacogene dezaparvovec continues to be generally well-tolerated with no treatment-related serious adverse events. No inhibitors to FIX have been reported and no consistent relationship between safety and pre-existing NAb titers has been observed.

“We continue to be very encouraged by the data generated from the HOPE-B pivotal study of etranacogene dezaparvovec, which have been accepted for presentation at the annual International Society on Thrombosis and Haemostasis congress taking place next month,” stated Ricardo Dolmetch, Ph.D., president of research and development at uniQure. “The 52-week data show mean FIX activity in the normal range and increase our confidence in the potential durability and long-term benefits of etranacogene dezaparvovec, bringing us one step closer to our goal of delivering this groundbreaking therapy to fulfill an unmet medical need for patients living with hemophilia B.”

Regulatory Update

The Company and its partner, CSL Behring, have had recent communications with U.S. Food and Drug Administration (FDA), including a pre-biologics licensing application (BLA) submission meeting held on June 4, 2021. The FDA confirmed that the primary evidence of durability of effect to inform regulatory decision-making will come from patients followed for at least a 52-week period beginning when etranacogene dezaparvovec-derived FIX levels have achieved steady state, rather than when etranacogene dezaparvovec is administered. This feedback was based upon review of statistical analysis plans, as no clinical data was provided or discussed. All patients in the HOPE-B pivotal study achieved steady-state FIX activity levels by 26-weeks after administration of etranacogene dezaparvovec. As a result, uniQure will now conduct as the sole primary endpoint a non-inferiority analysis of annualized bleeding rates (ABR) at 78 weeks after the administration (approximately 52-weeks after steady-state is achieved). The Company expects all patients to complete their 78-week follow-up visits by the end of the third quarter of 2021, and the Company and CSL Behring expect to submit the BLA in first quarter of 2022.

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