~ Largest gene therapy study in hemophilia B achieved primary endpoint of non-inferiority in annualized bleeding rate after stable Factor IX (FIX) expression, assessed at 18 months following a single dose of etranacogene dezaparvovec ~

~ Etranacogene dezaparvovec also achieved secondary endpoint demonstrating statistical superiority in reduction of annualized bleeding rate compared to baseline FIX prophylactic therapy ~

~ Stable and durable FIX levels with mean FIX activity of 36.9 percent of normal in full study population at 18-months, compared to a mean of 39.0 percent of normal at 6 months ~

~ Manufacturing operations supporting process validation of etranacogene dezaparvovec successfully completed by uniQure ~

LEXINGTON, Mass. and AMSTERDAM, The Netherlands and KING OF PRUSSIA, Pa., Dec. 09, 2021 (GLOBE NEWSWIRE) -- CSL Behring, a global biotherapeutics leader, and uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced that etranacogene dezaparvovec, an investigational adeno-associated virus five (AAV5)-based gene therapy for the treatment of patients with severe to moderately severe hemophilia B, achieved the pre-specified primary endpoint of non-inferiority in annualized bleeding rate (ABR) 18-months following administration compared to baseline Factor IX (FIX) prophylactic therapy in the pivotal Phase III HOPE-B gene therapy trial. The study also successfully achieved a secondary endpoint demonstrating statistical superiority in reduction of ABR compared to baseline FIX prophylactic therapy.

The primary endpoint in the pivotal study was 52-week ABR after achievement of stable FIX expression compared with the six-month lead-in period, considering all bleeds regardless of investigator adjudication as true bleeds. For this endpoint, ABR was measured from month seven to month 18 after infusion, ensuring the observation period represented likely steady-state FIX transgene expression. Secondary endpoints included assessment of FIX activity and statistical superiority of ABR after dosing.

“We are very pleased with these top-line results from what is the largest and first pivotal trial of a gene therapy for patients with hemophilia B,” stated Ricardo Dolmetsch, Ph.D., president of research and development at uniQure. “The HOPE-B data not only achieved the pre-specified primary endpoint of non-inferiority in annualized bleeding rate following 12 months or more of stable FIX expression, but also the secondary endpoint of superiority in reduction of annualized bleeding, while continuing to demonstrate durability and stability in FIX levels and other benefits to this point in the study.”

“On behalf of uniQure, we extend our heartfelt gratitude to all the HOPE-B clinical trial patients and their families, as well as the trial investigators,” he continued. “We now look forward to collaborating with CSL Behring on completing the regulatory submissions that we hope will advance etranacogene dezaparvovec one step closer to reaching hemophilia B patients around the world.”

uniQure led the multi-year clinical development of etranacogene dezaparvovec prior to entering into a Commercialization and License Agreement with CSL Behring in June 2020 for exclusive global rights to etranacogene dezaparvovec. Earlier this month, uniQure successfully completed manufacturing operations supporting process validation of etranacogene dezaparvovec.

Etranacogene dezaparvovec has been granted Breakthrough Therapy Designation by the United States Food and Drug Administration and access to Priority Medicine (PRIME) regulatory initiative by the European Medicines Agency. CSL Behring plans to submit regulatory applications for marketing approval of etranacogene dezaparvovec in the United States and European Union in the first half of 2022.

Top-line Data Results

A total of 54 patients received a single dose of etranacogene dezaparvovec in the pivotal trial, with 53 patients completing at least 18 months of follow-up.

ABR for all bleeds after stable FIX expression, assessed at 18 months, was 1.51 compared with the ABR of 4.19 for the lead-in period of at least six months, achieving the primary non-inferiority endpoint and a secondary superiority endpoint (p=0.0002) in the HOPE-B trial. ABR for investigator-adjudicated FIX-treated bleeds was 0.83 compared with lead-in ABR of 3.65 (p