uniQure N.V. (NASDAQ: QURE), a leading gene therapy company
advancing transformative therapies for patients with severe medical
needs, today announced updated interim data including up to 30
months of follow-up from 39 patients enrolled in the ongoing U.S.
and European Phase I/II clinical trials of AMT-130 for the
treatment of Huntington’s disease.
“The clinical assessment trends in the ongoing
studies of AMT-130 look very promising and continue to show disease
stability in Huntington’s disease patients treated with this
one-time administered gene therapy, several of whom have now been
followed more than two years,” stated Walid Abi-Saab, M.D., chief
medical officer of uniQure. “We are observing favorable trends in
evaluation of motor skills, functional independence, and composite
rating scores as compared to a non-concurrent criteria-matched
natural history cohort.”
“We also are pleased to observe further declines
in levels of NfL, a measurement of neuronal degradation and disease
progression, with low-dose patients below baseline at 30 months of
follow-up and high-dose patients near baseline at 18 months,” he
continued. “Importantly, AMT-130 continues to be generally
well-tolerated with a manageable safety profile at both its low and
high doses. We will continue to follow these patients and look
forward to initiating regulatory interactions next year.”
“The results from these Phase I/II trials
continue to be very encouraging as they show positive-trending,
potentially dose-dependent signals across multiple key clinical and
functional measures, in conjunction with further declines in NfL,”
stated Edward Wild, Ph.D., FRCP, professor of neurology at
University College London (UCL) Queen Square Institute of
Neurology, consultant neurologist at National Hospital for
Neurology & Neurosurgery, and associate director of UCL
Huntington’s Disease Centre. “While there are well-known
complexities associated with analyzing and interpreting other
biomarkers in Huntington’s disease, these NfL data are consistent
with the clinical data suggesting possible disease stability and
support the continued development of AMT-130. The Huntington’s
disease community has endured a prolonged and challenging wait for
disease-modifying treatment options, and we enthusiastically
embrace this potentially important advancement for this devastating
disease.”
Ongoing Phase I/II Trials of AMT-130 in
Huntington’s Disease
In the multi-center, Phase I/II clinical trial
of AMT-130 being conducted in the U.S., a total of 26 patients with
early-manifest Huntington’s disease have been enrolled, including
an initial 10-patient low-dose cohort (6 treated, 4 control) with
up to 30 months of follow-up and a subsequent 16-patient high-dose
cohort (10 treated, 6 control) with up to 18 months of follow-up.
Patients were randomized to treatment with AMT-130 or an imitation
(sham) surgery. The U.S. study consists of a blinded 12-month core
study period followed by unblinded long-term follow-up of five
years for treated patients. Four of the six control patients in the
high-dose cohort were crossed over to treatment and the remaining
two patients failed to meet the study’s inclusion criteria.
The multi-center, open-label, Phase I/II
clinical trial of AMT-130 being conducted in Europe and the UK
enrolled a total of 13 patients with the same early manifest
criteria for Huntington’s disease as the U.S. study. Six patients
were treated with AMT-130 in the initial low-dose cohort and seven
patients were treated in the subsequent high-dose cohort.
The combined U.S. and European data presented in
this release are subject to a September 30, 2023 cut-off date and
do not include efficacy and biomarker data from the control
patients who crossed over to treatment.
Updated Interim Data
Exploratory Efficacy Data
Clinical and functional measurements for treated
patients in each dose cohort were compared to baseline
measurements, as well as to control patients (up to 12 months) and
a non-concurrent criteria-matched natural history cohort. The
natural history cohort was developed by uniQure in collaboration
with the Cure Huntington’s Disease Initiative (CHDI) using the
TRACK-HD natural history study of patients with early Huntington’s
disease. The cohort includes 31 patients that met the uniQure
clinical trial inclusion criteria of Total Functional Capacity,
Diagnostic Classification Level and minimum striatal volumes.
- Updated clinical data through 30
months for the low-dose cohort and 18 months for the high-dose show
ongoing evidence of potential dose-dependent clinical benefit
relative to the non-concurrent criteria-matched natural
history.
- For patients receiving the high
dose, neurological function as measured by cUHDRS and each of its
individual components was preserved or improved at 18 months
compared to pre-treatment baseline measurements.
- For patients receiving the low
dose, neurological function as measured by Total Motor Score (TMS)
and Total Functional Capacity (TFC) was preserved at 30 months
compared to pre-treatment baseline measurements.
- When compared to the expected rate
of decline from the natural history cohort, AMT-130 showed
favorable trends in cUHDRS, TFC and TMS.
- composite Unified Huntington’s
Disease Rating Scale (cUHDRS): AMT-130 showed a favorable
difference in cUHDRS of 0.39 points at 30 months and 1.24 points at
18 months for the low- and high-dose, respectively (baseline
values: 14.1 in low-dose and 14.9 in high-dose).
- Total Functional Capacity (TFC):
AMT-130 showed a favorable difference in TFC of 0.95 points at 30
months in the low-dose and 0.49 points at 18 months in the
high-dose (baseline values: 11.9 in low-dose and 12.2 in
high-dose).
- Total Motor Score (TMS): AMT-130
showed a favorable difference in TMS of 2.80 points at 30 months in
the low-dose and 1.70 points in the high-dose at 18 months
(baseline values: 13.3 in low-dose and 12.1 in high-dose).
Biomarkers and Volumetric Imaging Data
- Neurofilament Light Chain (NfL):
Mean CSF NfL for the low-dose cohort remained below baseline
through month 30 and was 6.6% below baseline. Mean CSF NfL for the
high-dose cohort also further declined and is near baseline at
month 18. These data suggest a reduction in neurodegeneration when
compared to an expected increase from baseline in CSF NfL based on
natural history data. As expected, all patients treated with
AMT-130 experienced a transient increase in CSF NfL related to the
surgical procedure that peaked at approximately one month following
the procedure and declined thereafter. These transient increases
were not dose-dependent.
- Mutant Huntingtin Protein (mHTT):
Given AMT-130 is directly administered deep within the brain, the
pharmacodynamics of mHTT in the CSF are not believed to be
materially representative of mHTT in the targeted brain regions.
Mean changes in mHTT levels measured in CSF samples compared to
baseline continue to be variable and impacted by baseline levels
near or below the lower limit of quantification.
- Total Brain Volume: Changes in the
total brain volume of patients treated with AMT-130 were observed
after the surgical procedure and trended below natural history. The
volumetric changes do not appear to be clinically meaningful or
associated with protracted increases in neurodegeneration as
measured by NfL.
Safety and Tolerability
AMT-130 was generally well-tolerated, with a
manageable safety profile at both the lower dose of 6x1012 vector
genomes and the higher dose of 6x1013 vector genomes. The most
common adverse events in the treatment groups were related to the
surgical procedure.
There were four serious adverse events (SAE)
unrelated to AMT-130 (post-operative delirium, major depression,
suicidal ideation and epistaxis) in the low-dose cohort, six
unrelated SAEs in the high-dose cohort (back pain, hypothermia,
post procedural hematoma, post-lumbar puncture syndrome (n=2),
pulmonary embolism), and one SAE (deep vein thrombosis) in the
control group. In addition, there were four AMT-130-related serious
adverse events in the high-dose cohort (central nervous system
inflammation (n=3), and severe headache (1) that, retrospectively,
also was attributable to central nervous system inflammation.
Patients with symptomatic central nervous system
inflammation improved with glucocorticoid medication. Additionally,
six high-dose patients have received perioperative steroids with
the administration of AMT-130 to reduce the risk of
inflammation.
Next Steps
Based on the promising data from this interim
analysis, uniQure anticipates the following next steps:
- uniQure began enrolling patients in
a third cohort to further investigate both doses in combination
with perioperative immune suppression with a focus on evaluating
near-term safety. Up to 12 patients will be treated in this cohort,
all of whom will receive AMT-130 using the current, established
stereotactic neurosurgical delivery procedure.
- In the first quarter of 2024,
uniQure plans to initiate regulatory interactions to discuss the
U.S. and European data and potential strategies for ongoing
development of AMT-130.
- In mid-2024, uniQure expects to
present another clinical update from the ongoing Phase I/II studies
of AMT-130, including additional follow-up data from the treated
patients in the U.S. and European trials.
Investor Conference Call and Webcast
Information
uniQure management will host an investor
conference call and webcast today, Tuesday, December 19, 2023
at 8:30 a.m. ET. The event will be webcast under the Events
& Presentations section of uniQure’s website at
https://www.uniqure.com/investors-media/events-presentations, and
following the event a replay will be archived for 90 days.
Interested parties participating by phone will need to register
using this online form. After registering for dial-in details, all
phone participants will receive an auto-generated e-mail containing
a link to the dial-in number along with a personal PIN number to
use to access the event by phone. If you are joining the conference
call, please dial in 15 minutes before the start time.
About the Phase I/II Clinical Program of
AMT-130
The U.S. Phase I/II clinical trial of
AMT-130 for the treatment of Huntington’s disease is exploring the
safety, tolerability, and efficacy signals in 26 total patients
with early manifest Huntington’s disease split into a 10-patient
low-dose cohort followed by a 16-patient high-dose cohort; patients
are randomized to treatment with AMT-130 or an imitation (sham)
surgery. The multi-center trial consists of a blinded 12-month core
study period followed by unblinded long-term follow-up for five
years. A total of 16 patients in the clinical trial were randomized
to treatment and received a single administration of AMT-130
through MRI-guided, convection-enhanced stereotactic neurosurgical
delivery directly into the striatum (caudate and putamen). An
additional four control patients in the high-dose cohort crossed
over to treatment. Additional details are available on
www.clinicaltrials.gov (NCT04120493).
The European, open-label Phase Ib/II study of
AMT-130 enrolled 13 patients with early manifest Huntington’s
disease across two dose cohorts; a low-dose cohort of six patients
and a high-dose cohort of seven patients. Together with
the U.S. study, the European study is intended to
establish safety, proof of concept, and the optimal dose of AMT-130
to take forward into Phase III development or into a confirmatory
study should an accelerated registration pathway be
feasible.
AMT-130 is uniQure’s first clinical program
focusing on the CNS incorporating its proprietary
miQURE® platform.
About Huntington’s Disease
Huntington’s disease is a rare, inherited
neurodegenerative disorder that leads to motor symptoms including
chorea, behavioral abnormalities and cognitive decline resulting in
progressive physical and mental deterioration. The disease is an
autosomal dominant condition with a disease-causing CAG repeat
expansion in the first exon of the huntingtin gene that leads to
the production and aggregation of abnormal protein in the brain.
Despite the clear etiology of Huntington’s disease, there are no
currently approved therapies to delay the onset or to slow the
disease’s progression.
About uniQure
uniQure is delivering on the promise of gene
therapy – single treatments with potentially curative results. The
recent approvals of uniQure’s gene therapy for hemophilia B – an
historic achievement based on more than a decade of research and
clinical development – represent a major milestone in the field of
genomic medicine and usher in a new treatment approach for patients
living with hemophilia. uniQure is now leveraging its modular and
validated technology platform to advance a pipeline of proprietary
gene therapies for the treatment of patients with Huntington's
disease, refractory temporal lobe epilepsy, ALS, Fabry disease, and
other severe diseases. www.uniQure.com
uniQure Forward-Looking
Statements
This press release contains forward-looking
statements within the meaning of Section 27A of the Securities Act
of 1933, as amended, and Section 21E of the Securities Exchange Act
of 1934, as amended. All statements other than statements of
historical fact are forward-looking statements, which are often
indicated by terms such as "anticipate," "believe," "could,"
“establish,” "estimate," "expect," "goal," "intend," "look forward
to", "may," "plan," "potential," "predict," "project," “seek,”
"should," "will," "would" and similar expressions and the negatives
of those terms. 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. Examples
of these forward-looking statements include, but are not limited
to, statements concerning: the potential clinical and functional
effects of AMT-130, including as an important treatment option for
patients with Huntington’s disease; the company’s plans to continue
clinical development of AMT-130 and to initiate interactions with
regulatory authorities; the potential for accelerated regulatory
pathways; the company’s use of a natural history cohort as a basis
for comparison with respect to the efficacy of AMT-130; the
company’s enrollment plans with respect to the third cohort
studying AMT-130 in combination with perioperative immune
suppression; the utility of mHTT or NfL in CSF as an effective
biomarker; and the company’s plans for further clinical updates.
uniQure’s actual results could differ materially from those
anticipated in these forward-looking statements for many
reasons. These risks and uncertainties include, among others:
risks related to the company’s Phase I/ll clinical trials of
AMT-130, including the risk that such trials will be unable to
demonstrate efficacy data sufficient to support further clinical
development and the risk that interim data from the trials may not
be predictive of later data readouts; risks related to the
company’s financial position and stock price, including the
company’s ability to raise sufficient capital to support further
development of the company’s clinical programs, as needed and on
acceptable terms; risks related to the company’s reliance on third
parties to conduct, supervise, and monitor its preclinical studies
and clinical trials and to manufacture components of its drug
product, including the clinical trials for AMT-130; and the
company’s ability to obtain, maintain and protect its intellectual
property. These risks and uncertainties are more fully described
under the heading "Risk Factors" in uniQure’s periodic
filings with the U.S. Securities & Exchange Commission (SEC),
including its Annual Report on Form 10-K filed with the SEC on
February 27, 2023, its Quarterly Reports on Form 10-Q filed with
the SEC on May 9, 2023, August 1, 2023 and November 7, 2023, and in
other filings that the company makes with the SEC from time to
time. Given these risks, uncertainties and other factors, you
should not place undue reliance on these forward-looking statements
and, except as required by law, uniQure assumes no obligation to
update these forward-looking statements, even if new information
becomes available in the future.
uniQure Contacts:
FOR INVESTORS:Maria E.
CantorDirect: 339-970-7536Mobile:
617-680-9452m.cantor@uniQure.com |
Chiara RussoDirect: 617-306-9137Mobile:
617-306-9137c.russo@uniQure.com |
FOR MEDIA:Tom MaloneDirect:
339-970-7558Mobile: 339-223-8541t.malone@uniQure.com |
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