uniQure 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.
About the HOPE-B Pivotal Clinical
Trial
The pivotal Phase III HOPE-B trial is a
multinational, open-label, single-arm study to evaluate the safety
and efficacy of etranacogene dezaparvovec. Fifty-four adult
hemophilia B patients classified as severe or moderately severe
(defined as less than or equal to 2% of normal FIX activity) and
requiring prophylactic FIX replacement therapy were enrolled in a
prospective, six-month observational period during which time they
continued to use their current standard of care therapy to
establish a baseline ABR. After the six-month lead-in period,
patients received a single intravenous administration of
etranacogene dezaparvovec at the 2x1013 gc/kg dose. Patients were
not excluded from the trial based on their pre-existing NAbs to
AAV5. Forty-three percent of patients in the study had pre-existing
NAbs to AAV5 up to a maximum observed pre-dosing titer of over
3,200.
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). 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.
uniQure and CSL Behring entered into a commercialization and
license agreement providing CSL Behring exclusive global
commercialization rights to etranacogene dezaparvovec. The
collaboration combines uniQure’s differentiated gene therapy
candidate in hemophilia B and CSL Behring’s strong global reach and
commercial infrastructure in hematology in an effort to accelerate
access of etranacogene dezaparvovec to hemophilia B patients around
the world.
AAV5-based gene therapies have been demonstrated
to be safe and well tolerated in a multitude of clinical trials,
including being well-tolerated to date in six uniQure trials
conducted in nearly 90 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.
About uniQure
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
StatementsThis press release contains forward-looking
statements. All statements other than statements of historical fact
are forward-looking statements, which are often indicated by terms
such as "anticipate," "believe," "could," "estimate," "expect,"
"goal," "intend," "look forward to", "may," "plan," "potential,"
"predict," "project," "should," "will," "would" and 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 limited to, whether patients in the
Hope-B pivotal trial will complete their 78-week follow-up visits
by the end of the third quarter of 2021, whether CSL Behring will
submit a BLA for etranacogene dezaparvovec in the first quarter of
2022, whether the clinical data proves to be meaningful for the
long-term outlook for hemophilia gene therapy or etranacogene
dezaparvovec, whether etranacogene dezaparvovec has the potential
to provide well-tolerated, long-term clinical benefits, and whether
AAV5-based gene therapies can provide clinical benefit to patients
with pre-existing neutralizing antibodies. Our actual results could
differ materially from those anticipated in these forward-looking
statements for many reasons, including, without limitation, risks
associated with the impact of the ongoing COVID-19 pandemic on our
Company and the wider economy and health care system, our
Commercialization and License Agreement with CSL Behring, our and
our collaborators’ clinical development activities, clinical
results, collaboration arrangements, corporate reorganizations and
strategic shifts, regulatory oversight, product commercialization
and intellectual property claims, as well as the risks,
uncertainties and other factors described under the heading "Risk
Factors" in uniQure’s periodic securities filings, including is
Annual Report on Form 10-K filed March 2, 2020 and Quarterly Report
on Form 10-Q filed on May 10, 2021. Given these risks,
uncertainties and other factors, you should not place undue
reliance on these forward-looking statements, and we assume no
obligation to update these forward-looking statements, even if new
information becomes available in the future.
uniQure Contacts
FOR INVESTORS: |
|
FOR MEDIA: |
|
|
|
Maria E.
Cantor
Direct: 339-970-7536 Mobile:
617-680-9452 m.cantor@uniQure.com |
Chiara
Russo
Direct: 617-306-9137 Mobile:
617-306-9137 c.russo@uniQure.com
|
Tom MaloneDirect:
339-970-7558Mobile:339-223-8541t.malone@uniQure.com |
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