YASTEST
~ AMT-060 with the
FIX-Padua Modification (AMT-061) Demonstrates Substantial Increase
in FIX Activity in Non-human Primates ~
~ Plans to
Initiate Pivotal Study with Enhanced AMT-061 in 2018 ~
~ Achieves
Alignment with FDA on Streamlined Clinical and Regulatory Strategy
for AMT-061, Which Will be Included Under Existing Breakthrough
Therapy Designation ~
~ Acquires a
Patent Family Covering FIX-Padua in Hemophilia B ~
~ Conference Call
Scheduled for Today at 8:30 a.m. ET ~
LEXINGTON, Mass. and AMSTERDAM, The Netherlands,
Oct. 19, 2017 (GLOBE NEWSWIRE) -- uniQure N.V. (NASDAQ:QURE),
a leading gene therapy company advancing transformative therapies
for patients with severe medical needs, today announced that
following multi-disciplinary meetings with the U.S. Food and Drug
Administration (FDA) and the European Medicines Agency (EMA), the
company plans to expeditiously advance AMT-061, which combines an
AAV5 vector with the FIX-Padua mutant, into a pivotal study in 2018
for patients with severe and moderately severe hemophilia B.
AMT-061 and AMT-060, the latter of which has been
tested in 10 patients in an ongoing Phase I/II clinical trial, are
identical in structure apart from two nucleotide substitutions in
the coding sequence for FIX. The gene variant, referred to as
FIX-Padua, expresses a protein with a single amino acid
substitution that has been reported in multiple preclinical and
nonclinical studies to provide an approximate 8 to 9-fold increase
in FIX activity compared to the wild-type FIX protein. All other
critical quality attributes of AMT-061 are expected to be
comparable to those of AMT-060, as AMT-061 utilizes the same AAV5
capsid and proprietary insect cell-based manufacturing
platform.
"Our mission in hemophilia B has always been to
develop the safest and most effective gene therapy with the
broadest application to patients. We believe AMT-061 moves us
closer to this goal, as it has the potential to provide optimized
clinical and tolerability benefits to nearly all severe and
moderately severe patients with hemophilia B," stated Matthew
Kapusta, chief executive officer of uniQure. "We are
delighted to have received constructive guidance from both the FDA
and EMA, which we believe allows us to expeditiously advance
AMT-061 into a pivotal study next year, as previously planned. In
anticipation of this, we have begun GMP production of AMT-061 in
our Lexington facility and preparations for the pivotal study are
underway."
"I believe AMT-061 has the potential to be an
important gene therapy for patients suffering with hemophilia B,"
stated Steven Pipe, M.D., professor of pediatrics and pathology and
pediatric medical director of the hemophilia and coagulation
disorders program at the University of Michigan. "Based on the data
generated to date, AMT-061 may be the first gene therapy to provide
durable, curative benefits to nearly all patients with hemophilia
B, without the complications associated with capsid-related immune
responses. I very much look forward to serving as an
investigator in this exciting Phase III program."
Clinical and Regulatory Pathway for AMT-061
-
The FDA has agreed that AMT-061 will be included
under the existing Breakthrough Therapy designation and
Investigational New Drug (IND) for AMT-060. The EMA also has agreed
that AMT-061 will be included under the current PRIME
designation.
-
The Company achieved general agreement with the
FDA and EMA on the proposed pivotal trial plan for AMT-061. The
study is expected to be an open-label, single-dose, multi-center,
multi-national trial investigating the efficacy and safety of
AMT-061 administered to adult patients with severe or moderately
severe hemophilia B. The primary objective of the trial is to
evaluate AMT-061 for prevention of bleedings. Secondary objectives
include additional efficacy and safety aspects. Patients will serve
as their own control, with a baseline established during a
six-month observational lead-in phase prior to treatment with
AMT-061.
-
Concurrent with the start of the six-month
lead-in phase of the pivotal study, a short dose-confirmation study
is expected to begin in the third quarter of 2018. Three patients
will receive a single intravenous (IV) dose of AMT-061 at 2 x
1013 gc/kg and
will be evaluated for a period of approximately six weeks to assess
FIX activity levels and confirm the dose. Each patient will
continue to be followed longer term, and no lead-in phase is
required for the dose confirmation study.
AMT-061 Nonclinical Data Demonstrate Tolerability
and Substantial Increases in FIX Activity
-
A Good Laboratory Practices (GLP), nonclinical
study of AMT-061 has been performed in non-human primates at four
different dose levels up to a dose of 9 x 1013 gc/kg.
The purpose of this study was to compare AMT-061 to AMT-060 with
respect to liver transduction, circulating FIX protein levels,
circulating FIX activity levels and toxicity, after a single
intravenous dose with 13- or 26-week observation periods.
-
Data from the study demonstrated a strong
correlation between dose and human FIX (hFIX) expression levels, as
well as biological activity of the expressed hFIX protein. At
equal doses, circulating vector DNA plasma levels, liver
distribution, liver cell transduction and hFIX protein expression
were comparable for both AMT-060 and AMT-061. Additionally,
AMT-061 demonstrated substantial increases in hFIX clotting
activity compared to AMT-060, consistent with those previously
reported for FIX-Padua.
-
Based on a statistical analysis of the AMT-061
and AMT-060 non-human primate data, as well as the clinical data
from the Phase I/II trial of AMT-060, the Company believes that
AMT-061 administered at a dose of 2 x 1013 gc/kg may
lead to mean FIX activity of approximately 30 to 50 percent of
normal.
-
The study also examined toxicology of AMT-061,
including liver enzyme activity, coagulation biomarkers and other
safety parameters. Data from the study demonstrated that
AMT-061 was well-tolerated with no evidence of any significant
toxicological findings. There was no increased thrombin
generation or increased fibrin formation or degradation detected
during the six months of follow-up. No
increase in immunogenicity is expected with AMT-061, as there are
no changes in the AAV5 capsid.
AMT-061 Continues to Leverage AAV5's Favorable
Tolerability and Immunogenicity Results
-
AAV5-based gene therapies have been demonstrated
to be generally safe and well-tolerated in a multitude of clinical
trials, including three uniQure trials conducted in 22 patients in
hemophilia B and other indications.
-
In contrast to data reported using other AAV
capsids delivered systemically via IV infusion, no patient treated
in clinical trials with the Company's AAV5 gene therapies has
experienced any confirmed, T-cell-mediated immune response to the
capsid or material loss of FIX activity.
-
An independent clinical trial has demonstrated
that AAV5 has the lowest prevalence of preexisting neutralizing
antibodies (NAb) compared to other AAV vectors. Data from the
Phase I/II study of AMT-060 also demonstrated clinical
proof-of-concept in the presence of preexisting NAb to AAV5,
suggesting that all, or nearly all hemophilia B patients may be
eligible for treatment with AMT-061.
Commercial-scale, GMP Manufacturing of AMT-061
Clinical Material Underway
-
uniQure has initiated production of multiple
clinical-grade batches of AMT-061 in its state-of-the-art
Lexington, MA manufacturing facility. Material is being produced at
commercial scale and utilizing current Good Manufacturing Practices
(cGMP). uniQure expects to begin releasing product for the
pivotal trial by the first quarter of 2018. The manufacturing
process, controls and methods utilized for AMT-061 are consistent
to those previously used for AMT-060.
-
The Company has achieved alignment with the FDA
and EMA on its plan to establish comparability between AMT-061 and
AMT-060. uniQure expects to complete its ongoing
comparability analysis and plans to submit the data to the agencies
for review in the first quarter of 2018. Data reviewed to date
support comparability between AMT-061 and AMT-060.
Exclusive Patent Covers the Use of Padua in Gene
Therapy for Hemophilia B
-
In a separate press release, uniQure today
announced that it has acquired a patent family that broadly covers
the FIX-Padua variant and its use in gene therapy for the treatment
of coagulopathies, including hemophilia B. This family includes a
patent issued in the U.S., as well as pending patent applications
in Europe and Canada. uniQure recently filed divisional
patent applications that would further strengthen its intellectual
property position related to the FIX-Padua variant.
-
The patent family was acquired from Professor
Paolo Simioni, a renowned hemophilia expert at the University of
Padua, Italy, who is widely recognized as the first to identify the
mutation. Professor Simioni is serving as an advisor and consultant
exclusively to uniQure for the development of gene therapy products
using his invention. He is expected to assist the Company in
its discussions with regulators, investigators and key opinion
leaders throughout the clinical development of AMT-061.
Conference Call
Information
uniQure will host a conference call today, October
19, 2017 at 8:30 a.m. ET to discuss this announcement. To
access the live call by phone, dial (877) 280-2296 (United States)
or +44 (0)20 3427 1900 (international); the conference ID is
2516119. The call may also be accessed through the Investors
section of the Company's website at www.uniQure.com.
Following the live webcast, a replay of the call will be
available at the same location through November 2, 2017.
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, Huntington's disease and cardiovascular
diseases. www.uniQure.com
uniQure Forward-Looking
Statements
This 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 development of our gene therapy product candidates, the success
of our collaborations and the risk of cessation, delay or lack of
success of any of our ongoing or planned clinical studies and/or
development of our product candidates, and the scope of protection
provided by our patent portfolio. 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, 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
August 8, 2017. 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:
Maria E. Cantor
Direct: 339-970-7536
Mobile: 617-680-9452
m.cantor@uniQure.com
Eva M. Mulder
Direct: +31 20 240 6103
Mobile: +31 6 52 33 15 79
e.mulder@uniQure.com
For Media:
Tom Malone
Direct: 339-970-7558
Mobile: 339-223-8541
t.malone@uniQure.com
This
announcement is distributed by Nasdaq Corporate Solutions on behalf
of Nasdaq Corporate Solutions clients.
The issuer of this announcement warrants that they are solely
responsible for the content, accuracy and originality of the
information contained therein.
Source: uniQure N.V. via Globenewswire
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