uniQure and CSL Behring Announce Primary Endpoint Achieved in
HOPE-B Pivotal Trial of Etranacogene Dezaparvovec Gene Therapy in
Patients with Hemophilia B
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<0.0001).
Data from the HOPE-B pivotal trial showed that
patients continued to demonstrate durable, sustained increases in
FIX activity at 18 months post-infusion with a mean FIX activity of
36.9 percent of normal as measured by a one-stage APTT-based
clotting assay, compared to mean FIX activity of 39.0 percent of
normal at six months post-infusion.
Etranacogene dezaparvovec was generally
well-tolerated with over 80% of adverse events considered mild. One
death resulting from urosepsis and cardiogenic shock in a
77-year-old patient at 65-weeks following dosing was considered
unrelated to treatment by investigators and the company sponsor. A
serious adverse event of hepatocellular carcinoma (HCC) was
identified in one patient. Independent molecular characterization
and vector integration analysis of the HCC and adjacent tissue
supported the conclusion by the investigator and company sponsor
that the HCC was unrelated to treatment with etranacogene
dezaparvovec. No inhibitors to FIX were reported.
“These encouraging results illustrate the
potential that gene therapy has to be a long-term treatment option
for patients living with hemophilia B and we look forward to
sharing more detailed data with the medical community in the near
future,” stated Brahm Goldstein, MD, MCR, Vice President, Research
and Development, Hematology at CSL Behring. “This milestone
advances our efforts towards expected regulatory submissions in
first half of 2022.”
HOPE-B Pivotal Trial Design
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 annualized bleeding rate. No prophylactic
immunosuppression was provided to patients upon entering the study.
After the six-month lead-in period, patients received a single
intravenous administration
of etranacogene dezaparvovec at the
2x10^13 gc/kg dose. Patients were not excluded from the
trial based on pre-existing neutralizing antibodies
(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 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
temporal lobe epilepsy, Alzheimer’s, Parkinson’s and ALS.
www.uniQure.com
About CSL BehringCSL Behring is
a global biotherapeutics leader driven by our promise to save
lives. Focused on serving patients’ needs by using the latest
technologies, we discover, develop and deliver innovative therapies
for people living with conditions in the immunology, hematology,
cardiovascular and metabolic, respiratory, and transplant
therapeutic areas. We use three strategic scientific platforms of
plasma fractionation, recombinant protein technology, and cell and
gene therapy to support continued innovation and continually refine
ways in which products can address unmet medical needs and help
patients lead full lives.
CSL Behring operates one of the world’s largest
plasma collection networks, CSL Plasma. Our parent company, CSL
Limited (ASX:CSL; USOTC:CSLLY), headquartered in Melbourne,
Australia, employs more than 25,000 people, and delivers its
lifesaving therapies to people in more than 100 countries. For
inspiring stories about the promise of biotechnology, visit
CSLBehring.com/Vita and follow us on Twitter.com/CSLBehring.
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 CSL Behring will submit a BLA
for etranacogene dezaparvovec in the first half of
2022, whether etranacogene dezaparvovec will reach hemophilia
B patients around the world, and
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 its Annual Report on Form 10-K filed March 2,
2020 and Quarterly Report on Form 10-Q filed on October 25,
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. CantorDirect: 339-970-7536Mobile:
617-680-9452m.cantor@uniQure.com |
Chiara RussoDirect: 617-306-9137Mobile:
617-306-9137c.russo@uniQure.com |
Tom MaloneDirect: 339-970-7558Mobile:
339-223-8541t.malone@uniQure.com |
CSL Behring Contact:
Jennifer
PurdueMobile:
610-306-9355jennifer.purdue@cslbehring.com
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