-- Second-dose Cohort Demonstrates Dose Response
with All Patients Free of Prophylactic FIX Replacement Therapy
and Only One Spontaneous Bleed Reported
uniQure N.V. (Nasdaq:QURE), a leader in human gene therapy,
today announced new and 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 52 weeks of follow-up from
the low-dose cohort and up to 31 weeks of follow-up from the second
dose cohort.
New data presented from the second-dose cohort show a dose
response with substantial improvement in disease state in all five
patients, including the discontinuation of precautionary Factor IX
(FIX) infusions in all four patients that previously required
chronic replacement therapy. To date, only one spontaneous
bleed was reported after discontinuation of prophylactic FIX
replacement therapy.
All five patients in the low-dose cohort, who bleedings
were previously uncontrolled despite being managed with
prophylactic therapy, continue to maintain robust, constant
and clinically meaningful levels of FIX activity for up to 52
weeks post treatment, with a complete cessation of spontaneous
bleedings in the last 14 weeks of observation.
These clinical data from both patient cohorts were presented
last evening in a poster session of the 58th American Society
of Hematology (ASH) Annual Meeting taking place in San Diego,
California. "The data from this ongoing study
demonstrate clinically significant and sustained increases in
FIX activity, substantial reductions in FIX
replacement usage and a near cessation of spontaneous bleeding
episodes," stated Professor Frank W.G. Leebeek, M.D. Ph.D.
of the Erasmus University Medical Center in Rotterdam, the
Netherlands. "Importantly, at both doses evaluated, AMT-060
appears to be 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.
"In total, we are observing 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 still experienced many bleeds despite
prophylaxis with FIX," he added. "The safety and clinical
efficacy profile observed in this study, together with the
higher FIX expression levels support selection of the 2x1013 gc/kg
dose for a pivotal registration trial."
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 safety and broad applicability due to the low
prevalence 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.
- There were no screening failures due to pre-existing anti-AAV5
NABs in the study.
Key Data Update from Phase I/II Clinical Trial of AMT-060 in
Hemophilia B Patients Data as of October 15,
2016:
- 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, only one spontaneous bleeding
episode was reported over a period of 96 weeks of combined patient
observation, representing a reduction in the annualized spontaneous
bleed rate of 76% compared to the one-year period prior to
administration of AMT-060.
- Bleeding data was also evaluated from the low-dose cohort.
The frequency of spontaneous bleeds declined significantly
over time, with no spontaneous bleeds reported by any patient in
their last 14 weeks of observation. With up to 52 weeks of
follow-up, the annualized spontaneous bleed rate for the four
patients that discontinued prophylactic FIX infusions was reduced
by 59% compared to the one year period prior to administration of
AMT-060. The one patient in the low-dose cohort that remained on
prophylaxis also experienced a 45% reduction in spontaneous
bleeds.
- Eight of nine patients in the study that required chronic FIX
infusions prior to administration of AMT-060, including all such
patients in the second dose cohort, discontinued prophylaxis and
remained prophylaxis-free at the last follow up (22-52 weeks).
- Among the four patients in the low-dose cohort that
discontinued prophylaxis, annualized consumption of FIX concentrate
following AMT-060 administration was reduced substantially by more
than a cumulative total of 1,329,000 international units (85%),
compared to their pre-trial usage levels. The one
patient who remained on prophylactic FIX therapy in the low-dose
cohort has reduced frequency of bleeding episodes and also requires
materially less FIX concentrate after treatment with
AMT-060.
- Through up to 6 months of follow-up among the five patients in
the second-dose cohort, the mean steady-state FIX activity was
approximately 7% of normal, with expression up to a FIX activity of
13% of normal.
- In both dose cohorts, FIX activity remained consistent and
stable through up to one year of follow up with no emergence
of late immune response or loss of FIX activity in any of the
patients.
- AMT-060 continues to be well-tolerated, and there have been no
severe adverse events.
- Three out of the total of 10 patients (two in the second-dose
cohort and one previously reported from the low-dose cohort)
experienced mild, asymptomatic elevations of alanine
aminotransferase (ALT) and received a tapering course of
corticosteroids per protocol. Importantly, the temporary
elevations in ALT were not associated with any loss of
endogenous FIX activity or T-cell response.
- No patients across either cohort have developed inhibitory
antibodies against FIX, or demonstrated sustained AAV5
capsid-specific T-cell activation.
- AMT-060 continues to demonstrate a very low screening failure
rate, with all patients screened in the study testing negative
for pre-existing anti-AAV5 NABs. To date, 25 patients have
been screened for pre-existing anti-AAV5 NABs with a fully
validated assay across several clinical studies with only one
patient excluded due to a borderline positive result.
This collective data set suggests that a
large proportion of the hemophilia patient population may be
eligible for treatment with AMT-060.
"The data from our Phase I/II study demonstrate AMT-060 is
delivering sustained and significantly improved clinical benefits
to patients suffering from severe hemophilia B by enabling
them to discontinue frequent infusions of FIX replacement
therapy and to essentially eliminate the risk of spontaneous
bleeding," stated Christian Meyer, M.D., Ph.D., chief medical
officer at uniQure. "Importantly, none of the patients
treated with AMT-060 have lost FIX activity for up to one year post
administration. To date, our insect-cell manufactured AAV5
gene therapies have been administered to 22 patients across three
clinical studies without any evidence of AAV5 capsid-specific
cellular immune responses or long-term safety complications."
"The proprietary elements of AMT-060, including our
fully-humanized FIX gene cassette and AAV5 vector, are the only
gene therapy components clinically demonstrated in hemophilia B to
be safe, effective, and durable for up to six and a half years," he
added. "We believe these factors, along with our
commercial-scale manufacturing capabilities, differentiate AMT-060
from other hemophilia gene therapies in development, and we look
forward to advancing our program into a late-stage clinical study."
AMT-060 is being co-developed with Chiesi for Europe.
Investor/Analyst Breakfast and Webcast on
Monday, December 5, 2016 uniQure management will
host an investor breakfast meeting featuring Professor Leebeek to
review the updated data on AMT-060 and outline progress taking
place with its ongoing clinical development. The
meeting will be webcast live along with slides and can be
accessed by visiting the investor relations section of
the Company's website at www.uniQure.com
Date and
Time: Monday, December 5, 2016 at
7:00 am PST/ 10:00 am ESTLocation:
Marriott Gaslamp Hotel, Room Presidio C, 660 K Street, San Diego,
CA 92101
To request attendance at the meeting, please RSVP to
Investors@uniQure.com as space is limitedAbout 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 CNS, liver/metabolic and cardiovascular diseases.
www.uniQure.com
uniQure Forward-Looking Statement
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 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 2015 Annual Report on Form 20-F
filed with the Securities and Exchange Commission on April 4, 2016.
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.comTom MaloneDirect:
339-970-7558Mobile: 339-223-8541t.malone@uniQure.com
Eva M.
MulderDirect: +31 20 240 6103Mobile: +31 6 52 33 15 79
e.mulder@uniQure.com
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