uniQure Announces Updated, Long-Term Clinical Data from Ongoing Phase I/II Trial of AMT-060 In Patients with Severe Hemophili...
July 10 2017 - 12:46PM
Clinical Benefit Maintained in All Patients, with
FIX Activity Persisting At Up To 18 Months of Follow-Up
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
BHemophilia 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
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, 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.
uniQure Contacts:
Maria E. Cantor
Direct: 339-970-7536
Mobile: 617-680-9452
m.cantor@uniqure.com
Tom Malone
Direct: 339-970-7558
Mobile: 339-223-8541
t.malone@uniQure.com
Eva M. Mulder
Direct: +31 20 240 6103
Mobile: +31 6 52 33 15 79
e.mulder@uniQure.com
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