Full Press Release Details
Update on Phase I/II Clinical Trials of AMT-130
for the Treatment of Huntington's Disease
~ Patients treated with AMT-130 continue to
show evidence of preserved neurological function with potential dose-dependent clinical benefits relative to an inclusion criteria-matched
natural history of the disease ~
~ Mean CSF NfL continue to demonstrate favorable
trends with low-dose patients below baseline at 30 months and high-dose patients near baseline at 18 months ~
~ AMT-130 continues to be generally well-tolerated
~ Data support continuing clinical development
of AMT-130 and pursuing regulatory interactions to discuss potential strategies for ongoing development ~
~ Investor conference call and webcast today
Lexington, MA and Amsterdam, the Netherlands,
December 19, 2023 - 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
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
and Volumetric Imaging Data
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.
Based on the promising
data from this interim analysis, uniQure anticipates the following next steps:
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