AMT-130 / uniQure - LARVOL DELTA

Huntington's disease clinical trials update: March 2025. (PubMed, J Huntingtons Dis) - "In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing phase I clinical trial of ALN-HTT02 from Alynlam Pharmaceuticals. We also report on the SAGE-718 (also known as dalzanemdor) program from Sage Therapeutics, with results of the phase II DIMENSION study and the recent termination of the open-label phase III PURVIEW study. Additionally, we discuss recent developments in the regulatory pathway for AMT-130, following discussions between uniQure and the U.S. Food and Drug Administration regarding key aspects of accelerated approval. Finally, we provide a comprehensive listing of all currently registered and ongoing clinical trials in Huntington's disease."

Journal • Huntington's Disease • Movement Disorders

Combined Targeting of HTT , HTT1a and Somatic Instability in Huntington's Disease using LinQURE®: a Feasibility Study in Multiple HD Mouse Models (ASGCT 2025) - "Many therapies that are under development, including uniQure's clinical-stage candidate AMT-130, are designed to lower HTT levels, with the goal of slowing neurodegeneration...Such approaches hold major promise as potential next-generation gene therapies for HD. Disease Focus of Abstract:Central Nervous System Disorders"

Preclinical • CNS Disorders • Gene Therapies • Huntington's Disease • Movement Disorders • MSH3

uniQure Announces FDA Breakthrough Therapy Designation Granted to AMT-130 for the Treatment of Huntington’s Disease (GlobeNewswire) - "uniQure N.V...today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to AMT-130 for the treatment of Huntington’s disease, a rare, inherited neurodegenerative disorder for which there are currently no disease-modifying therapies available....The Breakthrough Therapy designation is supported by clinical data from the ongoing Phase I/II trials of AMT-130 for the treatment of Huntington’s disease....Additional regulatory update and guidance on the Biologics License Application submission expected in the second quarter of 2025."

Breakthrough therapy • FDA filing • Huntington's Disease

UniQure Shares Soar After Latest FDA Designation for Huntington's Disease Treatment (Market Watch) - "Gene therapy developer uniQure shares soared 46% in premarket trading after its treatment for Huntington's disease received breakthrough therapy designation from the Food and Drug Administration. Shares were trading around $13.70. The stock has doubled over the last year. The Netherlands-based company said the FDA's designation for AMT-130 is in addition to the regenerative medicine advanced therapy designation, orphan drug designation and fast track designation previously granted by the regulator."

Stock price • Huntington's Disease

CT-AMT-130-01: Safety and Proof-of-Concept (POC) Study with AMT-130 in Adults with Early Manifest Huntington's Disease (clinicaltrials.gov) - P1/2 | N=37 | Active, not recruiting | Sponsor: UniQure Biopharma B.V. | Recruiting ➔ Active, not recruiting

Enrollment closed • Huntington's Disease • Movement Disorders • NEFL

Huntington's Disease Clinical Trials Update: September 2024. (PubMed, J Huntingtons Dis) - "In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing extension study of PTC518 from PTC Therapeutics, including 12-month interim results from the parent study. We also discuss 24-month interim results from uniQure's AMT-130 program and 28-week follow-up results from Wave Life Sciences' SELECT-HD clinical trial of WVE-003. Additionally, we provide a comprehensive listing of all currently registered and ongoing clinical trials in Huntington's disease."

Journal • Review • Huntington's Disease • Movement Disorders

CT-AMT-130-01: Safety and Proof-of-Concept (POC) Study with AMT-130 in Adults with Early Manifest Huntington's Disease (clinicaltrials.gov) - P1/2 | N=37 | Recruiting | Sponsor: UniQure Biopharma B.V. | Active, not recruiting ➔ Recruiting

Enrollment open • Huntington's Disease • Movement Disorders • NEFL

uniQure Announces Alignment with FDA on Key Elements of Accelerated Approval Pathway for AMT-130 in Huntington’s Disease (GlobeNewswire) - "uniQure N.V...today announced that the company reached agreement with the U.S. Food and Drug Administration (FDA) on key elements of an Accelerated Approval pathway for AMT-130...'We have initiated BLA readiness activities and look forward to further engaging with the FDA in the first half of 2025 to discuss our statistical analysis plan and the technical CMC requirements.' As part of uniQure’s Regenerative Medicine Advanced Therapy (RMAT) Type B meeting held in late November, the FDA agreed that data from the ongoing Phase I/II studies, compared to a natural history external control, may serve as the primary basis for a BLA submission under the Accelerated Approval pathway...The FDA also agreed that cUHDRS may be used as an intermediate clinical endpoint and that reductions in neurofilament light chain (NfL) measured in cerebrospinal fluid (CSF) may serve as supportive evidence of therapeutic benefit in the application for accelerated approval."

FDA event • FDA filing • CNS Disorders • Huntington's Disease

CT-AMT-130-02: Safety and Efficacy of AMT-130 in European Adults with Early Manifest Huntington's Disease (clinicaltrials.gov) - P1/2 | N=14 | Active, not recruiting | Sponsor: UniQure Biopharma B.V. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Huntington's Disease • Movement Disorders • CHI3L1 • GFAP • NEFL

uniQure Announces Third Quarter 2024 Financial Results and Highlights Recent Company Progress (GlobeNewswire) - "Advancing AMT-130 for the treatment of Huntington’s disease:...The Company will also discuss with the FDA a future communication plan that is expected to include additional sub-disciplinary meetings to take place in the first half of 2025...Patient dosing is ongoing in a third cohort of up to 12 patients to further evaluate both doses of AMT-130 together with an immunosuppression regimen, with a focus on evaluating near-term safety and tolerability. Enrollment in this third cohort is expected to be completed in the fourth quarter of 2024. The Company expects to provide an additional interim update from its ongoing Phase I/II clinical trials of AMT-130 in mid-2025."

Enrollment status • FDA event • P1/2 data • CNS Disorders • Huntington's Disease

Safety and Proof-of-Concept (POC) Study with AMT-130 in Adults with Early Manifest Huntington's Disease (clinicaltrials.gov) - P1/2 | N=36 | Active, not recruiting | Sponsor: UniQure Biopharma B.V. | Recruiting ➔ Active, not recruiting

Enrollment closed • Huntington's Disease • Movement Disorders • NEFL

Exon 1-targeting miRNA reduces the pathogenic exon 1 HTT protein in Huntington disease models. (PubMed, Brain) - "The effects were confirmed in primary Hu128/21 neuronal cultures. These results demonstrate that AAV5-miHTT gene therapy is an effective approach to lower both FL HTT and the pathogenic HTTexon1 levels, which could potentially have an additive therapeutic benefit compared to other HTT-targeting modalities."

Journal • CNS Disorders • Gene Therapies • Genetic Disorders • Huntington's Disease • Movement Disorders

uniQure Announces Positive Interim Data Update Demonstrating Slowing of Disease Progression in Phase I/II Trials of AMT-130 for Huntington’s Disease (GlobeNewswire) - P1/2 | N=26 | NCT04120493 | P1/2 | N=13 | NCT05243017 | Sponsor UniQure Biopharma B.V. | "uniQure N.V...today announced updated interim data including up to 24 months of follow-up data from 29 treated patients enrolled in the ongoing U.S. and European Phase I/II clinical trials of AMT-130 for the treatment of Huntington’s disease....A statistically significant, dose-dependent, slowing in disease progression measured by cUHDRS was observed through 24 months in patients receiving the high dose of AMT-130. At 24 months, the mean change in cUHDRS for patients receiving the high-dose of AMT-130 was -0.2 compared to -1.0 for patients in the propensity score-weighted external control, representing an 80% slowing of disease progression (p=0.007). At 24 months, the mean change in cUDHRS for patients receiving the low-dose of AMT-130 was -0.7 compared to -1.0 for patients in the propensity score-weighted external control..."

P1/2 data • CNS Disorders • Genetic Disorders • Huntington's Disease

uniQure Announces Positive Interim Data Update Demonstrating Slowing of Disease Progression in Phase I/II Trials of AMT-130 for Huntington’s Disease (GlobeNewswire) - "Based on the encouraging data from this interim analysis, uniQure anticipates the following next steps: In the second half of 2024, uniQure expects to hold a Type B, multi-disciplinary RMAT meeting with U.S. Food and Drug Administration (FDA) to present these updated data and discuss potential expedited clinical development pathways and accelerated approval. In the second half of 2024, uniQure expects to complete enrollment of the third cohort of the U.S. Phase I/II study exploring AMT-130 in combination with immunosuppression. In the first half of 2025, uniQure anticipates presenting safety data from this cohort. In mid-2025, uniQure expects to present another interim analysis from the ongoing Phase I/II studies of AMT-130. The data will include a 36-month comparison of treated patients to the propensity score-weighted external control."

FDA event • P1/2 data • Trial status • CNS Disorders • Genetic Disorders • Huntington's Disease

uniQure Announces Positive Interim Data Update Demonstrating Slowing of Disease Progression in Phase I/II Trials of AMT-130 for Huntington’s Disease (GlobeNewswire) - P1/2 | N=26 | NCT04120493 | P1/2 | N=13 | NCT05243017 | Sponsor UniQure Biopharma B.V. | "A statistically significant reduction of NfL in cerebrospinal fluid (CSF) was observed in patients treated with AMT-130. Patients treated with AMT-130 had a mean reduction in CSF NfL of 11% compared to baseline (p=0.02) at 24 months. Mean CSF NfL levels for both high and low doses were below baseline at 24 months. CSF NfL is a well-characterized biomarker of neurodegeneration that has been shown to be strongly associated with the clinical severity of Huntington’s disease. An independent natural history study demonstrated a 26% increase in CSF NfL at 24 months in patients with early manifest Huntington’s disease (n=19)."

P1/2 data • CNS Disorders • Genetic Disorders • Huntington's Disease

uniQure Receives FDA Regenerative Medicine Advanced Therapy (RMAT) Designation for Investigational Gene Therapy AMT-130 in Huntington’s Disease (GlobeNewswire) - "uniQure N.V...announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation for its investigational gene therapy AMT-130 for the treatment of Huntington’s disease....uniQure expects to provide updated interim data from the ongoing Phase I/II U.S. and European studies of AMT-130 in the middle of 2024. The interim update will include up to three years of follow-up on 29 treated patients, 21 of which will have been followed for at least two years."

FDA event • P1/2 data • CNS Disorders • Genetic Disorders • Huntington's Disease

uniQure Announces First Quarter 2024 Financial Results and Highlights Recent Company Progress (GlobeNewswire) - "Patient dosing is ongoing in a third cohort of up to 12 patients to further evaluate both doses of AMT-130...Enrollment in this third cohort is expected to be completed in the second half of 2024....AMT-162 for the treatment of SOD1 amyotrophic lateral sclerosis (ALS) – Patient enrollment in a Phase I/II clinical trial is expected to begin in the third quarter of 2024."

Enrollment status • Trial status • Amyotrophic Lateral Sclerosis • CNS Disorders • Huntington's Disease

Safety and Efficacy of AMT-130 in European Adults With Early Manifest Huntington's Disease (clinicaltrials.gov) - P1/2 | N=15 | Recruiting | Sponsor: UniQure Biopharma B.V. | Trial completion date: Oct 2027 ➔ Oct 2029 | Trial primary completion date: Mar 2027 ➔ Mar 2029

Trial completion date • Trial primary completion date • Genetic Disorders • Huntington's Disease • Movement Disorders • CHI3L1 • GFAP • NEFL

Understanding Pharmacy Costs and the Changing Treatment Landscape in Huntington's Disease (HD) in the US: A Systematic Literature Review (SLR) and Database Review for Disease-Modifying Therapies (DMT) in Development (ISPOR 2024) - "Motor symptoms incur the greatest annual drug cost, with high median costs per patient (2019) for tetrabenazine ($24,996), deutetrabenazine ($69,972), and valbenazine ($76,908). Ten clinical trials are investigating potential future DMTs: two-antisense oligonucleotides (n=5; Tominersen [RO7234292, ISIS 443139], WVE-003), two-RNA-targeting small molecules (n=2; PTC518, Branaplam), monoclonal antibodies (n=2; ANX005, VX15/2503), and gene therapy (n=1; rAAV5-miHTT). Pharmacy costs for symptomatic treatment are substantial in HD, with these costs increasing as HD progresses and symptom severity increases. This significant burden illustrates the importance of developing new DMTs that can prevent or slow disease progression for patients with HD."

Review • CNS Disorders • Depression • Gene Therapies • Huntington's Disease • Mood Disorders • Movement Disorders • Psychiatry

Huntington's Disease Clinical Trials Update: February 2024. (PubMed, J Huntingtons Dis) - "In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing program from VICO Therapeutics and on the recently terminated VIBRANT-HD clinical trials. We also discuss updates from uniQure's AMT-130 program and PTC therapeutics' trial of PTC518 and list all currently registered and ongoing clinical trials in Huntington's disease."

Journal • Genetic Disorders • Huntington's Disease • Movement Disorders

uniQure Announces 2023 Financial Results and Highlights Recent Company Progress (GlobeNewswire) - "In the second quarter of 2024, the Company expects to initiate regulatory interactions with the U.S. Food and Drug Administration (FDA) to discuss data from the ongoing Phase I/II studies and potential strategies for the further development of AMT-130. By the end of 2024, the Company expects to have greater clarity regarding a potential approval pathway for AMT-130. In mid-2024, the Company expects to provide an interim update from the ongoing Phase I/II studies of AMT-130, including up to 24- and 36-month follow-up data from all treated patients in the U.S. and European trials."

FDA event • P1/2 data • CNS Disorders • Huntington's Disease

uniQure Announces Update on Phase I/II Clinical Trials of AMT-130 Gene Therapy for the Treatment of Huntington’s Disease (GlobeNewswire) - "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."

European regulatory • FDA event • P1/2 data • Trial status • CNS Disorders • Genetic Disorders • Huntington's Disease

uniQure Announces Update on Phase I/II Clinical Trials of AMT-130 Gene Therapy for the Treatment of Huntington’s Disease (GlobeNewswire) - P1/2 | N=36 | NCT04120493 | Sponsor: UniQure Biopharma B.V. | "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..."

P1/2 data • CNS Disorders • Genetic Disorders • Huntington's Disease

uniQure Announces Third Quarter 2023 Financial Results and Highlights Recent Company Progress (GlobeNewswire) - "In the first quarter of 2024, the Company plans to request regulatory interactions with the Food and Drug Administration (FDA) to discuss the U.S. and EU data and potential late-stage development pathways for AMT-130....AMT-162 for the treatment of SOD1 amyotrophic lateral sclerosis (ALS)....The Company expects to initiate patient screening in the fourth quarter of 2023 with first patient dosing planned to occur in the first quarter of 2024."

European regulatory • FDA event • New trial • Amyotrophic Lateral Sclerosis • CNS Disorders • Huntington's Disease

uniQure Announces Major Presence at the European Society of Gene and Cell Therapy (ESGCT) Annual Meeting (GlobeNewswire) - "uniQure N.V...today announced that 12 data presentations, including two oral presentations, will be delivered at the European Society of Gene and Cell Therapy (ESGCT) Annual Meeting being held October 24-27 in Brussels, Belgium."

P1/2 data • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Huntington's Disease