Full Press Release Details
Announces Two-Year Follow-Up Data from the Phase IIb Study of Etranacogene
Dezaparvovec and Long-Term Follow-Up Data for AMT-060 in Patients with Hemophilia B
~ Sustained FIX Activity at Therapeutic
Levels1 with a Mean of 44% of Normal at Two Years
After Administration of Etranacogene Dezaparvovec
in Phase IIb Study ~
~ Long-term Clinical Benefit and Tolerability
Maintained in All Patients
Through up to Five Years of Follow-Up in
Phase I/II Study of AMT-060 ~
Lexington, MA and Amsterdam, the Netherlands,
December 7, 2020 - uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative
therapies for patients with severe medical needs, today announced updated clinical data on the three patients treated in uniQure's
ongoing Phase IIb study of etranacogene dezaparvovec, an investigational AAV5-based gene therapy containing a patent-protected
FIX-Padua variant for the treatment of patients with severe and moderately severe hemophilia B. These clinical data were
presented today in an oral presentation at the virtual 62nd Annual Meeting of the American Society of Hematology (ASH).
In addition, uniQure presented up to 5 years of follow-up data on the 10 patients in the Phase I/II trial of AMT-060, its first-generation
gene therapy for the treatment of hemophilia B, in a poster presentation at the meeting. The oral presentation slides and poster are available in the Investor Relations section of uniQure's website at www.uniQure.com under
At Least Two Years of Stable, Therapeutic
Levels of FIX Activity in Patients Treated with Etranacogene Dezaparvovec
The Phase IIb study of etranacogene dezaparvovec
is an open-label, single-dose, single-arm, multi-center trial being conducted in the United States. Three patients with severe
hemophilia (endogenous Factor IX (FIX) activity less than or equal to one percent) were enrolled in the study and received a single
intravenous infusion of 2x1013 gc/kg. Prior to the administration of etranacogene dezaparvovec, all three patients showed
low levels of pre-existing neutralizing antibodies to AAV5 but were not excluded from the trial on that basis. The patients in
the Phase IIb study have now been followed for two years to assess FIX activity, bleeding rates and usage of FIX replacement therapy,
and will be monitored for five years to evaluate the safety of etranacogene dezaparvovec.
In today's oral presentation at ASH,
two-year follow-up data show that all three patients have sustained FIX activity at therapeutic levels after the one-time administration
of etranacogene dezaparvovec. Mean FIX activity for the three patients at two years after administration was 44.2% of normal (compared
to 41% of normal at 52 weeks), with the first patient achieving FIX activity of 44.7% of normal, the second patient achieving FIX
activity of 51.6% of normal and the third patient achieving FIX activity of 36.3% of normal. The second and third patients had
previously screen-failed and were excluded from another gene therapy study due to pre-existing neutralizing antibodies to a different
AAV vector. Reported FIX activity was measured using an activated partial thromboplastin time (aPTT) assay performed at a central
data indicate that factor activity above 12% of normal is associated with substantial reduction or elimination of spontaneous bleeds
and factor usage. Den Uijl IE et al Haemophilia 2011; 17(6):849-53
At two years after dosing, two of the
three participants remain free from bleeds and use of FIX replacement therapy. A single bleed has been reported in one
participant, who has used a total of two FIX infusions (excluding surgery). All patients have remained free of prophylaxis in
the two years since receiving etranacogene dezaparvovec.
"These clinical data show that a
single administration of etranacogene dezaparvovec continues to be well tolerated by these patients through two years of follow-up
with the potential to achieve durable increases of FIX activity within the normal range," stated Annette von Drygalski, M.D.,
PharmD, director of the Hemophilia and Thrombosis Treatment Center at the University of California San Diego and a principal investigator
in the study. "The data offer encouraging support for the potential long-term benefits of etranacogene dezaparvovec, which
are being further characterized in the ongoing Phase 3 HOPE-B study."
"We are very pleased with these latest
results demonstrating long-term clinical benefits of etranacogene dezaparvovec in these patients," stated Ricardo Dolmetsch,
president of research and development at uniQure. "These data will be included in regulatory submissions to the FDA and EMA,
which we anticipate will begin in the second half of 2021, along with FIX activity and bleeding rates from the ongoing HOPE-B Phase
Stable FIX Expression and Durable Reductions
in Bleeding and FIX Consumption for up to 5 Years Following AMT-060 Gene Therapy
In the ongoing Phase I/II study of AMT-060,
all 10 patients continue to show long-term clinical benefit, including sustained increases in FIX activity, reduced usage of FIX
replacement therapy, and decreased bleeding frequency. At up to 5 years of follow-up, AMT-060 continues to be well-tolerated, with
no new treatment-related adverse events since the last reported data and no development of inhibitors during the study. This represents
the second-longest follow-up ever reported in a successful hemophilia gene therapy trial.
"In up to 5 years after a single
administration, the Phase I/II study of AMT-060 has now demonstrated clear evidence of long-term clinical benefits in these patients,
including sustained increases in FIX activity, improved disease phenotype and substantial reductions in bleeding," stated
Professor Frank W.G. Leebeek, M.D. Ph.D. of the Erasmus University Medical Center in Rotterdam, the Netherlands. "In addition,
the AAV5-based AMT-060 continues to demonstrate positive long-term data in this trial that appear to be meaningful for the long-term
outlook for hemophilia gene therapy and, in particular, etranacogene dezaparvovec."
All five patients in the second dose cohort
of 2x1013 gc/kg (the same dose being studied in the Phase III HOPE-B study of etranacogene dezaparvovec) continue to
be free of routine FIX replacement therapy at four-and-a-half years after treatment. Based on the six months of data collected
during the fifth year of follow-up, the mean annualized bleeding rate was zero compared to an average of 4 bleeds during the year
prior to treatment, representing a 100% reduction. During this same period, the usage of FIX replacement therapy declined to zero
compared to 354,800 IU in the year prior to treatment, representing a 100% reduction. Mean FIX activity over 4.5 years was 7.4%,
while in the lower dose cohort, mean FIX activity was 5.2% over 5 years since treatment.
AMT-060 is uniQure's first-generation
gene therapy, consisting of an AAV5 vector carrying a gene cassette with the wild-type FIX gene. Data from this Phase I/II trial
of AMT-060 also will be part of the regulatory submissions for marketing approval of etranacogene dezaparvovec.
About Etranacogene Dezaparvovec
Etranacogene dezaparvovec consists of an
AAV5 viral vector carrying a gene cassette with the patent-protected Padua variant of Factor IX (FIX-Padua). uniQure holds multiple
issued patents in the United States and Canada broadly covering methods of treating bleeding disorders, including hemophilia B,
using AAV gene therapy with the FIX-Padua variant. 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. In June 2020, the Company and CSL Behring entered into a licensing agreement providing CSL Behring with
exclusive global rights to etranacogene dezaparvovec. This licensing agreement is subject to antitrust regulatory review in the
United States, Australia and the United Kingdom that is currently ongoing.
AAV5-based gene therapies have been demonstrated
to be safe and well tolerated in a multitude of clinical trials, including being well tolerated in five uniQure trials conducted
in nearly 80 patients in hemophilia B and other indications. No patient treated in clinical trials with the uniQure's AAV5
gene therapies has experienced any confirmed cytotoxic T-cell-mediated immune response to the capsid. Additionally, pre-clinical
and clinical data show that AAV5-based gene therapies may be viable treatments in patients with pre-existing antibodies to AAV5,
thereby potentially increasing patient eligibility for treatment compared to other gene therapy product candidates.
uniQure is delivering on the promise of
gene therapy - single treatments with potentially curative results. We are leveraging our modular and validated technology
platform to rapidly advance a pipeline of proprietary gene therapies to treat patients with hemophilia B, Huntington's
disease, Fabry disease, spinocerebellar ataxia Type 3 and other diseases. www.uniQure.com
uniQure Forward-Looking Statements
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similar expressions. Forward-looking statements are based on management's beliefs and assumptions and on information
available to management only as of the date of this press release. These forward-looking statements include, but are not