– Clinical Benefit Maintained in All
Patients, with Durable Increases in FIX Clotting Activity at
Up to Two 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,
dose-ranging Phase I/II trial of AMT-060, its investigational gene
therapy in patients with severe hemophilia B. The data
includes up to two years of follow-up from the low-dose cohort and
up to 18 months of follow-up from the second, higher-dose cohort.
The AAV5-based AMT-060 remains safe and
well-tolerated with up to two years of follow-up, with no new
serious adverse events and no development of inhibitors. No patient
in the study has had any loss of Factor IX (FIX) activity or
capsid-specific, T-cell-mediated immune response.
Eighteen-month follow-up data from the
second-dose cohort continue to show stable FIX activity 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 89% to a mean of 0.3 bleeds after gene
transfer. In the last year of follow-up, no patient in the second
cohort has reported any spontaneous bleeds.
These clinical data were presented this morning
in an oral presentation at the 58th American Society of Hematology
(ASH) Annual Meeting taking place in Atlanta, Georgia.
"We continue to observe a therapeutic benefit
from AMT-060 that is clearly superior to patients’ previous
prophylactic FIX replacement therapy regimen, with stable
elevations in Factor IX levels and a 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, the AAV5-based AMT-060
remains safe and well-tolerated, with no loss of FIX activity, no
activation of T-cell response and no development of inhibitors for
any of the 10 patients in the study, up to two years after
treatment. The safety profile observed in this study continues
to suggest that the AAV5 vector offers long-term safety, efficacy
and the potential for broad application in hemophilia B
patients.”
uniQure announced in October that, following
meetings with the FDA and EMA, it plans to initiate a pivotal study
in 2018 with AMT-061, which combines an AAV5 vector with the
FIX-Padua mutant. AMT-061 and AMT-060 are identical in structure
apart from two nucleotide substitutions in the coding sequence for
FIX. The gene variant, referred to as FIX-Padua, has been
reported in multiple preclinical and nonclinical studies to provide
an approximate 8 to 9-fold increase in FIX clotting activity
compared to the wild-type FIX gene. 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.
“These data give us continued confidence that
our AAV5-based gene therapies offer multi-year durability, superior
safety and broad applicability as a result of a favorable
immunogenicity profile compared to other AAV vectors,” stated
Matthew Kapusta, chief executive officer of uniQure. “We
believe AMT-061 has the potential to provide curative benefits to
nearly all hemophilia B patients, without the complications
associated with capsid-related immune responses. Preparations for
the pivotal study are underway and the manufacturing of AMT-061 for
clinical use has been initiated.”
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.
- 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.
Data Update from Phase I/II Clinical Trial of
AMT-060 in Hemophilia B Patients
Data as of October 26,
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 have been
reported in the last year of follow-up, with a reduction in the
annualized spontaneous bleed rate of 89% compared to the one-year
period prior to administration of AMT-060. Total bleeds were
reduced by 75%.
- 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 84%, from 2.64 million to 428,554 IU.
- Through up to 18 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 (18 months) was 8.1%, ranging from 4.2% to
11.1%.
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, the development of our
gene therapy product candidates, the transition to our AMT-061
product candidate, 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 November 1, 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. CantorDirect: 339-970-7536Mobile:
617-680-9452m.cantor@uniqure.com
Tom MaloneDirect: 339-970-7558Mobile:
339-223-8541t.malone@uniQure.com
Eva M. MulderDirect: +31 20 240 6103Mobile: +31
6 52 33 15 79e.mulder@uniQure.com
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