Clinical Benefit Maintained in All Patients,
with FIX Activity Persisting At Up To 18 Months of Follow-Up
Second-dose Cohort Demonstrates Dose Response Up to One Year, with
84% Reduction in
Spontaneous Bleeds and All Patients Free of Prophylactic FIX
Replacement Therapy No Activation of T-Cell Responses or Loss of
FIX Activity in Any Patient Up To 18 Months
LEXINGTON, Mass. and AMSTERDAM,
the Netherlands, July 10, 2017 (GLOBE NEWSWIRE) -- uniQure
N.V. (NASDAQ:QURE), a leading gene therapy company advancing
transformative therapies for patients with severe medical needs,
will today announce updated results from its ongoing,
dose-ranging Phase I/II trial of AMT-060, its proprietary,
investigational gene therapy in patients with severe
hemophilia B. The data includes up to 18 months of follow-up from
the low-dose cohort and up to one year of follow-up from the second
dose cohort.
The AAV5-based AMT-060 remains
safe and well-tolerated with up to a year and a half of follow-up,
with no serious adverse events and no development of inhibitors.
All patients are now past one year of follow up with no loss of
Factor IX (FIX) activity and no capsid-specific T-cell
activation.
One-year follow-up data from the
second-dose cohort continue to show a dose response with
substantial improvement in disease state in all five patients,
including the discontinuation of routine prophylactic FIX infusions
in all patients that previously required chronic replacement
therapy. The annualized spontaneous bleeding rate for the second
dose cohort declined 84% to a mean of 0.5 annual bleeds after gene
transfer. During more than 1,700 cumulative patient days of
observation, only one patient in the second cohort reported two
unconfirmed spontaneous bleeds, and no such bleeds were reported by
any patient during the last six months of observation.
These clinical data will be
presented today in an oral presentation at the 26th Biennial
Congress of the International Society on Thrombosis and
Haemostasis (ISTH), taking place this week in Berlin, Germany.
"We continue to observe a
therapeutic benefit from AMT-060 that is clearly superior to their
previous prophylactic FIX replacement therapy regimen, even in
patients with advanced joint disease who experienced a high rate of
bleeds prior to gene transfer," stated Professor Wolfgang Miesbach,
M.D., of the University Hospital Frankfurt, Germany.
"Importantly, AMT-060 appears to
be safe and well-tolerated, and quite differentiated, with no
loss of FIX activity, no activation of T-cell response and no
development of inhibitors for any of the ten patients in the study.
The safety profile observed in this study suggests that the
AAV5 vector offers long-term safety, efficacy and the potential for
broad application in hemophilia B patients," he
added.
Phase 1/2 Trial
Overview
The AMT-060 gene therapy consists of a codon-optimized wild type
FIX gene cassette, the LP1 liver promoter and an AAV5 viral
vector manufactured by uniQure using its proprietary insect
cell-based technology platform. It is the only hemophilia gene
therapy that combines a gene cassette with clinically proven
multi-year durability, now out more than five years, and an
AAV5 vector serotype that has demonstrated superior safety and
broad applicability due to the low prevalence of
clinically-relevant titers of neutralizing antibodies (NABs) as
evaluated in more than 20 patients across clinical studies in
three different diseases.
- The Phase I/II, open-label,
multi-center study includes 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.
- Patients in the low-dose cohort were
characterized by poorly controlled bleeding manifestations despite
use of high-dose FIX replacement therapy during the year prior to
study compared to the second-dose cohort.
- All but one patient in the study
across both cohorts required chronic infusions of prophylactic
FIX therapy at the time of enrollment. The remaining patient, who
is in the second dose cohort, used FIX therapy on
demand.
Data Update from Phase I/II
Clinical Trial of AMT-060 in Hemophilia B Patients
Data as of
May 12, 2017:
- All 10 patients in the study have
demonstrated improvements in their disease state as measured by
reduced FIX replacement therapy and bleeding frequency.
- In the second-dose cohort, no
spontaneous bleeds were reported in the last six months of
follow-up, with a reduction in the annualized spontaneous bleed
rate of 84% compared to the one-year period prior to administration
of AMT-060. Total bleeds were reduced by
64%.
- As previously announced, eight of
the nine patients that required chronic FIX infusions prior to
administration of AMT-060 have discontinued prophylaxis after
treatment. All eight patients remained prophylaxis-free at the
last follow up.
- Across both dose cohorts, cumulative
annualized FIX consumption decreased by 79%, from 2.64 million to
544,741 IU.
- Through up to 12 months of follow-up
among the five patients in the second-dose cohort, the mean
steady-state FIX activity persisted at approximately 7% of normal.
The mean FIX activity at the last follow-up (52 weeks) was 8.82%,
ranging from 5.2% to 10.7%.
- AMT-060 continues to be
well-tolerated, and there have been no severe adverse
events.
- In both dose cohorts, FIX activity
remained consistent and stable through up to 18 months of follow-up
with no emergence of late immune response or loss of FIX
activity in any of the patients.
- As previously announced, three
patients experienced mild, asymptomatic elevations of alanine
aminotransferase (ALT) soon after administration. For these
patients, ALT levels returned to their baseline readings, no
recurrence of ALT elevation has occurred, and no loss of FIX
activity was observed.
- No patients across either cohort
have developed inhibitory antibodies against FIX, or
demonstrated sustained AAV5 capsid-specific T-cell
activation.
"The data from our Phase I/II
study demonstrate that AMT-060 continues to deliver sustained and
significantly improved clinical benefits over the long term to
patients suffering from severe hemophilia B," stated Matt Kapusta,
chief executive officer of uniQure. "Our AAV5-based gene therapy
has been clinically demonstrated to be safe, effective and durable,
with no loss of efficacy at up to 18 months of observation and no
cellular immune responses in any patient. Moreover, our use
of an AAV5 construct may enable us to offer the promise of gene
therapy to nearly all patients suffering from hemophilia B. We
continue to make significant progress preparing for our
manufacturing campaign and regulatory interactions to support a
potential pivotal study, and look forward to providing an update
later this year."
AMT-060 is being co-developed with
Chiesi for Europe.
About Hemophilia B
Hemophilia B is a serious and rare inherited disease in males
characterized by insufficient blood clotting. The condition can
lead to repeated and sometimes life-threatening episodes of
external and internal bleeding following accidental trauma or
medical interventions. Severe hemophilia is characterized by
recurrent episodes of spontaneous joint bleeds, that cause
long-term damage to the joints resulting in disabling arthropathy.
Bleeds may be fatal if they occur in the brain. The deficient blood
clotting results from the lack of functional human Factor IX, or
hFIX. Treatment of hemophilia B today consists of prophylactic or
on-demand protein replacement therapy, in which one to three times
weekly intravenous administrations of plasma-derived or recombinant
hFIX are required to prevent bleeding and once daily infusions in
case bleeding occurs. Hemophilia B occurs in approximately 1 out of
30,000 live births.
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, statements regarding the development of our gene
therapy product candidates, including the future development of
AMT-060, 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. Our actual results could differ materially from those
anticipated in these forward-looking statements for many reasons,
including, without limitation, risks associated with corporate
reorganizations and strategic shifts, collaboration arrangements,
our and our collaborators' clinical development activities,
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
2016 Annual Report on Form 10-K filed on March 15, 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.