-- Clinical Benefit of AMT-060 Maintained in All
Patients Through up to Two and a Half Years of Follow-up –
uniQure N.V. (NASDAQ: QURE), a leading gene therapy company
advancing transformative therapies for patients with severe medical
needs, today announced updated results from its ongoing Phase
I/II trial of AMT-060, and provided an update on AMT-061, the
Company’s next-generation gene therapy candidate currently in
late-stage clinical development for patients with hemophilia B.
AMT-060 is a first-generation gene therapy consisting of an AAV5
vector carrying a gene cassette with the wild-type FIX gene. The
data on AMT-060 includes up to two and a half years of follow-up
from the low-dose cohort and up to two years of follow-up from the
second, higher-dose cohort. These clinical data were
presented on Sunday, December 2 in a poster presentation at the
59th American Society of Hematology (ASH) Annual Meeting taking
place in San Diego, California.
AMT-060 continues to be safe and well-tolerated,
with no new serious adverse events and no development of
inhibitors. All 10 patients sustained increases in FIX activity and
improvements in their disease state as measured by reduced usage of
FIX replacement therapy and decreased bleeding frequency.
All five patients in the second dose cohort of
2x1013 gc/kg continue to be free of routine prophylaxis at up to
two years after treatment. During the last 12 months of
observation, the mean annualized bleeding rate was 0.5 bleeds,
representing an 88% reduction compared to the year prior to
treatment. During the same period, the usage of FIX
replacement therapy declined 93% compared to the year prior to
treatment. Mean FIX activity increased from 7.1% in the first
year after treatment to 8.3% in the second year and was 8.9% of
normal at the last measurement.
"With up to two and a half years of follow-up,
patients in the study continue to show evidence of durable clinical
benefits, including sustained FIX activity, substantial reductions
in the usage of replacement therapy and a near cessation of
spontaneous bleeds," stated Professor Frank W.G. Leebeek, M.D.
Ph.D. of the Erasmus University Medical Center in Rotterdam, the
Netherlands. "Most importantly, since the last data update at ASH
2017, the study continues to demonstrate the long-term safety and
tolerability of AAV5-based gene therapies, with no new
treatment-related adverse events, no toxic cellular immune
responses and no patients losing FIX activity.”
Advancing AMT-061 in Late-Stage Clinical
Development
The Company recently announced initial clinical
data in patients treated in a Phase IIb dose-confirmation study of
AMT-061, a next-generation, AAV5-based gene therapy containing a
patent protected FIX-Padua variant for the treatment of hemophilia
B. Six weeks after administration, mean FIX activity for the
three patients in the study was 31% of normal, and FIX levels
continue to increase beyond the initial six to ten weeks of follow
up. Based on the data obtained to date, no patient has
required any infusions of FIX replacement therapy, reported any
bleeding events or required any immunosuppression therapy.
The Data Monitoring Committee for the study has
now reviewed these initial data and confirmed the dose of 2x1013
gc/kg for administration in the HOPE-B Phase III pivotal trial. The
Company expects the dosing phase of the pivotal study to begin in
the first quarter of 2019.
“The long-term data from our Phase I/II study of
AMT-060 demonstrate the durability and safety of AAV5-based gene
therapies and bode well for the late-stage development of AMT-061,”
stated Matt Kapusta, chief executive officer of uniQure. “We
believe AMT-061, which has clinically demonstrated the potential to
provide functionally curative increases in FIX activity, may be a
best-in-class gene therapy for patients with hemophilia B, and we
look forward to treating our first patient in the pivotal study
early next year.”
About AMT-060 and AMT-061
AMT-060 is a first-generation gene therapy
consisting of an AAV5 vector carrying a gene cassette with the
wild-type FIX gene. In October 2017, the Company announced
the transition to AMT-061, which also consists of an AAV5 vector
including the Padua variant of Factor IX (FIX-Padua). AMT-060 and
AMT-061 are identical in structure apart from two nucleotide
substitutions in the coding sequence for FIX. FIX-Padua has been
reported in multiple preclinical and nonclinical studies to provide
an approximately 8 to 9-fold increase in FIX activity compared to
the wild-type FIX protein.
uniQure holds multiple issued patents in the
United States, the European Union and Canada broadly covering
methods of treating bleeding disorders, including hemophilia B,
using AAV gene therapy with the FIX-Padua variant. Additional
patents are pending in the United States and in the European
Union.
AAV5-based gene therapies have been demonstrated
to be safe and well-tolerated in a multitude of clinical trials,
including four uniQure trials conducted in 25 patients in
hemophilia B and other indications. No patient treated in clinical
trials with the Company’s AAV5 gene therapies has experienced any
reported cytotoxic T-cell-mediated immune response to the
capsid.
About the Phase I/II study of
AMT-060
The Phase I/II study is an open-label,
multi-center study including 10 patients each receiving a one-time,
30-minute, intravenous administration of AMT-060, without the
prophylactic use of corticosteroids. The study includes two dose
cohorts of five patients each, with the first cohort receiving
5x1012 gc/kg and the second cohort receiving 2x1013 gc/kg. Nine
patients in the trial were classified as having severe (<1% FIX
activity) hemophilia. One patient in the low-dose cohort had
a moderate/severe (1.5% FIX activity) phenotype.
About the Phase IIb study of
AMT-061
The Phase IIb study is an open-label,
single-dose, single-arm, multi-center trial being conducted in the
United States. Three patients with severe hemophilia were enrolled
in this study and received a single intravenous infusion of AMT-061
at a dose of 2x1013 vc/kg. Patients are evaluated for the presence
of pre-existing neutralizing antibodies to AAV5 but not excluded
from the trial on that basis. The objective of the study is to
evaluate the safety and tolerability of AMT-061 and confirm the
dose based on FIX activity at six weeks after administration.
Patients in the study will be followed for 52 weeks to assess FIX
activity, bleeding rates and usage of FIX replacement therapy, and
will be monitored for five years to evaluate the safety of AMT-061.
About the Phase III HOPE-B Pivotal
Study
The Phase III HOPE-B pivotal trial is a
multinational, multi-center, open-label, single-arm study to
evaluate the safety and efficacy of AMT-061. Approximately 50 adult
hemophilia B patients classified as severe or moderately severe
will be enrolled in a six-month observational period during which
time they will continue to use their current standard of care to
establish a baseline control. After the six-month lead-in period,
patients will receive a single intravenous administration of
AMT-061. Dosing of patients in the HOPE-B pivotal trial is expected
to start in the first quarter of 2019.
The primary endpoint of the study will be based
on the FIX activity level achieved following the administration of
AMT-061, and the secondary endpoints will measure annualized FIX
replacement therapy usage, annualized bleed rates and safety.
Patients enrolled in the HOPE-B trial will be
evaluated for the presence of pre-existing neutralizing antibodies
to AAV5 but will not be excluded from the trial on that basis.
Previous preclinical studies performed by uniQure suggest that AAV5
gene therapies may be viable treatments for at least 97% of
patients.
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 and partnered gene therapies to treat patients with
hemophilia B, hemophilia A, Huntington's disease, Fabry disease,
Spinocerebellar ataxia Type 3, and cardiovascular
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, the completion of our
Phase IIb study, the ability of AMT-061 to be a successful gene
therapy treatment for at least 97% hemophilia B patients or to
deliver sustained increases in FIX activity or to provide a
favorable immunogenicity profile or to eliminate the risk of an
immune response, the realization of FIX activity levels that
continue to be sustained or increased beyond the levels achieved in
the AMT-060 and AMT-061 studies, the determination that any of
AMT-060, AMT-061 and the AAV5 capsid used in those product
candidates are safe or effective or will be determined by any
regulatory body to be safe and effective, the risk of cessation,
delay or lack of success of any of our ongoing or planned clinical
studies such as the dosing of patients in the HOPE-B pivotal trial
in the first quarter of 2019 or at any time, and/or the development
and regulatory approval of our product candidates in the United
States or in Europe. Our actual results could differ materially
from those anticipated in these forward-looking statements for many
reasons, including, without limitation, risks associated with 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 Quarterly Report on Form 10-Q filed on
November 6, 2018. 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 |
Eva M. Mulder |
Tom Malone |
Direct: 339-970-7536 |
Direct: +31 20 240 6103 |
Direct: 339-970-7558 |
Mobile: 617-680-9452 |
Mobile: +31 6 52 33 15 79 |
Mobile: 339-223-8541 |
m.cantor@uniQure.com |
e.mulder@uniQure.com |
t.malone@uniQure.com |
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