Full Press Release Details
Regulatory Update on AMT-130 for Huntington's Disease
~ Alignment with FDA continues to support Accelerated
~ BLA submission planned for first quarter of
~ Conference call today at 8:30 a.m. ET
and Amsterdam, the Netherlands, June 2, 2025 - uniQure N.V. (NASDAQ: QURE), a leading gene therapy company
advancing transformative therapies for patients with severe medical needs, today provided a regulatory update on AMT-130, its investigational
gene therapy for the treatment of Huntington's disease. Following recent Type B meetings and further guidance from the U.S. Food
and Drug Administration (FDA), the Company has reached alignment with the FDA on several key components of the statistical analysis plan
and Chemistry, Manufacturing and Controls (CMC) information that will support a Biologics License Application (BLA) submission expected
in the first quarter of 2026.
pleased with our continued, productive engagement with the FDA and the progress we've made toward a planned BLA submission for
AMT-130 in the first quarter of 2026," said Walid Abi-Saab, M.D., chief medical officer of uniQure. "We are
pursuing an accelerated approval pathway supported by multiple years of clinical data - a rigorous and differentiated approach
that reflects the urgent need in Huntington's disease and our commitment to delivering the first disease-modifying treatment for
people affected by this devastating disease. We are grateful to the FDA for their continued engagement and look forward to sharing three-year
top-line data in the third quarter of 2025."
Statistical Analysis Plan
In the second quarter of 2025, the Company
held a Type B meeting with the FDA to discuss the proposed use of external control data and the prospectively defined statistical
analysis plan (SAP) in support of the planned BLA submission for AMT-130. The FDA continued to support its prior agreement that the
composite Unified Huntington's Disease Rating Scale (cUHDRS) may serve as an acceptable registrational, intermediate clinical
endpoint for accelerated approval. The FDA agreed that the primary efficacy analysis for the BLA will evaluate the 3-year change in
cUHDRS in high-dose AMT-130 patients compared to a propensity score-adjusted external control arm. The Company plans to use
propensity score-weighted external control derived from the ENROLL-HD dataset for the primary analysis and to submit certain
sensitivity analyses, including one using a propensity score-matched external control, as additional support.
The FDA also agreed that ENROLL-HD - a large,
prospective, longitudinal, natural history study of patients with Huntington's disease - may be acceptable as the external
control dataset for the primary analysis of the trial data along with additional sensitivity analyses using the TRACK-HD/TRACK-ON and
PREDICT-HD datasets. To date, approximately 33,000 patients have enrolled in ENROLL-HD. Compared to previously used natural history studies
like TRACK-HD and PREDICT-HD, ENROLL-HD offers a substantially larger sample size, lower attrition rates, and longer average patient follow-up.
The Company expects the larger sample size to reduce variability in the external control data and enhance the robustness of the SAP.
The Company plans to submit an updated SAP
consistent with discussions from the recently held Type B meeting to the FDA in the second quarter of 2025.
Chemistry, Manufacturing and Controls (CMC)
In the first quarter
of 2025, the Company held a Type B meeting with the FDA to discuss CMC requirements in support of the planned BLA submission for AMT-130.
The FDA agreed that validation of the AMT-130 manufacturing process should be possible using experience and prior knowledge from
the etranacogene dezaparvovec-drlb (HEMGENIX ) process, complemented with additional full-scale AMT-130 GMP batches and
a single Process Performance Qualification (PPQ) batch.
The FDA also agreed with the Company's proposed
drug product release testing plan, including the proposed potency assay, pending completion of qualification and specification setting
Next Steps for the Planned BLA Submission
Based on these recent
Type B meetings with the FDA, the Company continues to prepare for a BLA submission for AMT-130 in the treatment of Huntington's
disease. Certain key next steps and expected timing include:
Investor Conference Call and Webcast Information
will host an investor conference call and webcast today, Monday, June 2, 2025 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
uniQure is conducting two multi-center, dose-escalating,
Phase I/II clinical studies to explore the safety, tolerability, and exploratory efficacy signals of AMT-130 for the treatment of Huntington's
disease. In the U.S. study, a total of 26 patients with early manifest Huntington's disease were randomized to treatment (n=6 low
dose; n=10 high dose) or an imitation (sham) surgical procedure (n=10). Treated patients received a single administration of AMT-130 through
MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum (caudate and putamen). The study consists
of a blinded 12-month core study period followed by unblinded long-term follow-up of treated patients for five years. An additional four
control patients crossed over to treatment.
The European open-label Phase Ib/II study of AMT-130
enrolled 13 patients with early manifest Huntington's disease (n=6 low dose; n=7 high dose).
A third cohort enrolled an additional 12 patients
across sites in the U.S. and EU. This cohort was randomized to explore both doses of AMT-130 in combination with immunosuppression, using
the current, established stereotactic administration procedure.
are available on www.clinicaltrials.gov (NCT0543017, NCT04120493)
AMT-130 has been granted the FDA's Regenerative
Medicine Advance Therapy (RMAT) designation and Breakthrough Therapy designation, the first therapy for Huntington's disease to
receive an RMAT designation.
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. According to 2021
study in Neuroepidemiology, approximately 70,000 people have been diagnosed with Huntington's disease in the U.S. and Europe, with
hundreds of thousands of others at risk of inheriting the disease. Despite the clear etiology of Huntington's disease, there are
currently no approved therapies to delay the onset or to slow the disease's progression.
uniQure is delivering
on the promise of gene therapy - single treatments with potentially curative results. The 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 ushers in a new treatment approach for patients living with hemophilia. uniQure
is now advancing 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
as of the date of this press release. Examples of these forward-looking statements include, but are not limited to, statements concerning:
the availability of accelerated approval pathways and the need for additional pre-approval studies for AMT-130; the Company's anticipated
timing of the BLA submission; the Company's plans to submit a revised SAP and CMC information to the FDA; the Company's ability
to deliver a potentially life-changing therapy to people living with Huntington's disease and related timeline for doing so; the
potential clinical and functional effects of AMT-130; the Company's plans to continue clinical development of AMT-130; the Company's
plans to share clinical data of AMT-130 in the third quarter of 2025; and the utility of the ENROLL-HD patient dataset with respect to
Phase I/II study. The Company may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements.
Furthermore, the Company's actual results could differ materially from the plans, intentions and expectations anticipated in these
forward-looking statements for many reasons. These risks and uncertainties include, among others: risks related to the Company's