uniQure Announces Dosing of First Patient in Phase I/IIa Clinical Trial of AMT-191 for the Treatment of Fabry Disease
uniQure N.V. (NASDAQ: QURE) has initiated dosing in a Phase I/IIa clinical trial of AMT-191 for Fabry disease treatment. The multi-center, open-label trial in the US will assess safety, tolerability, and early efficacy signs in two dose-escalating cohorts. AMT-191 is an AAV5-based gene therapy delivering a galactosidase alpha (GLA) transgene to the liver. It aims to address the α-galactosidase A enzyme deficiency in Fabry patients.
The trial includes two cohorts of up to six adult male patients each, with low (6x10^13 gc/kg) and high (3x10^14 gc/kg) doses administered intravenously. Patients will be followed for 24 months. This milestone aligns with uniQure's goal to advance three new gene therapies into clinical studies this year, alongside programs in Huntington's disease, temporal lobe epilepsy, and SOD1-ALS.
uniQure N.V. (NASDAQ: QURE) ha iniziato la somministrazione in uno studio clinico di fase I/IIa per il trattamento della malattia di Fabry con AMT-191. Lo studio multicentrico, aperto e condotto negli Stati Uniti valuterà la sicurezza, la tollerabilità e i segni precoci di efficacia in due coorti con dosaggi crescenti. AMT-191 è una terapia genica basata su AAV5 che consegna un transgene galattosidasi alfa (GLA) al fegato. L'obiettivo è affrontare la carenza dell'enzima α-galattosidasi A nei pazienti con Fabry.
Lo studio include due coorti di fino a sei pazienti maschi adulti ciascuna, con dosaggi bassi (6x10^13 gc/kg) e alti (3x10^14 gc/kg) somministrati per via endovenosa. I pazienti saranno seguiti per 24 mesi. Questo traguardo è in linea con l'obiettivo di uniQure di far avanzare tre nuove terapie genetiche negli studi clinici quest'anno, insieme ai programmi per la malattia di Huntington, l'epilessia temporale e la SOD1-ALS.
uniQure N.V. (NASDAQ: QURE) ha iniciado la administración en un estudio clínico de fase I/IIa para el tratamiento de la enfermedad de Fabry con AMT-191. El estudio multicéntrico, abierto y realizado en los EE. UU. evaluará la seguridad, la tolerabilidad y los signos tempranos de eficacia en dos cohortes de dosis escalonadas. AMT-191 es una terapia génica basada en AAV5 que entrega un transgen de galactosidasa alfa (GLA) al hígado. Su objetivo es abordar la deficiencia de la enzima α-galactosidasa A en pacientes con Fabry.
El ensayo incluye dos cohortes de hasta seis pacientes masculinos adultos cada una, con dosis bajas (6x10^13 gc/kg) y altas (3x10^14 gc/kg) administradas por vía intravenosa. Los pacientes serán monitoreados durante 24 meses. Este hito se alinea con el objetivo de uniQure de avanzar tres nuevas terapias génicas a estudios clínicos este año, junto con programas en la enfermedad de Huntington, la epilepsia del lóbulo temporal y la SOD1-ALS.
uniQure N.V. (NASDAQ: QURE)는 Fabry병 치료를 위한 AMT-191의 1상/2a 임상 시험에서 투여를 시작했습니다. 미국에서 진행되는 이 다센터 개방형 시험은 두 개의 용량 증가 집단에서 안전성, 내약성 및 초기 효능 징후를 평가할 예정입니다. AMT-191은 간에 galactosidase alpha (GLA) 전자를 전달하는 AAV5 기반 유전자 요법입니다. 이 치료법은 Fabry 환자에게서 α-galactosidase A 효소 결핍 문제를 해결하는 것을 목표로 합니다.
이 시험은 각 집단에 최대 6명의 성인 남성 환자가 포함되며, 저용량(6x10^13 gc/kg)과 고용량(3x10^14 gc/kg)을 정맥 주사로 투여합니다. 환자는 24개월 동안 추적 관찰됩니다. 이 이정표는 uniQure의 올해 Huntington병, 측두엽 간질, SOD1-ALS에 대한 치료 프로그램과 함께 세 가지 새로운 유전자 요법을 임상 연구로 발전시키려는 목표와 일치합니다.
uniQure N.V. (NASDAQ: QURE) a lancé l'administration dans un essai clinique de phase I/IIa pour le traitement de la maladie de Fabry avec AMT-191. L'essai multicentrique, ouvert, mené aux États-Unis évaluera la sécurité, la tolérabilité et les premiers signes d'efficacité dans deux cohortes à dosage croissant. AMT-191 est une thérapie génique basée sur AAV5 qui livre un transgène galactosidase alpha (GLA) au foie. Son objectif est de remédier à la déficience en enzyme α-galactosidase A chez les patients atteints de Fabry.
L'essai comprend deux cohortes de jusqu'à six patients mâles adultes chacune, avec des doses faibles (6x10^13 gc/kg) et élevées (3x10^14 gc/kg) administrées par voie intraveineuse. Les patients seront suivis pendant 24 mois. Cette étape s'aligne avec l'objectif d'uniQure de faire avancer trois nouvelles thérapies géniques vers des études cliniques cette année, en plus des programmes pour la maladie de Huntington, l'épilepsie du lobe temporal et la SOD1-ALS.
uniQure N.V. (NASDAQ: QURE) hat die Dosisvergabe in einer Phase I/IIa klinischen Studie mit AMT-191 zur Behandlung der Fabry-Krankheit eingeleitet. Die multizentrische, offene Studie in den USA wird Sicherheit, Verträglichkeit und erste Anzeichen von Wirksamkeit in zwei dosissteigernden Kohorten bewerten. AMT-191 ist eine auf AAV5 basierende Gentherapie, die ein Galaktosidase-alpha (GLA) Transgen an die Leber abgibt. Sie zielt darauf ab, die α-Galaktosidase-A-Enzymdefizienz bei Fabry-Patienten zu beheben.
Die Studie umfasst zwei Kohorten von bis zu sechs erwachsenen männlichen Patienten, bei denen niedrigere (6x10^13 gc/kg) und höhere (3x10^14 gc/kg) Dosen intravenös verabreicht werden. Die Patienten werden über 24 Monate hinweg beobachtet. Dieser Meilenstein steht im Einklang mit dem Ziel von uniQure, in diesem Jahr drei neue Gentherapien in klinische Studien vorzubringen, zusätzlich zu Programmen zur Huntington-Krankheit, zur Temporallappenepilepsie und zur SOD1-ALS.
- Initiation of Phase I/IIa clinical trial for AMT-191 in Fabry disease
- AMT-191 utilizes proven AAV delivery technology from HEMGENIX®
- Potential one-time intravenous treatment for Fabry disease
- Multiple pipeline catalysts expected across various programs
- Strong balance sheet with runway extended through end of 2027
- Early-stage clinical trial with uncertain outcomes
- patient population in initial trial (up to 12 adult male patients)
Insights
The initiation of the Phase I/IIa trial for AMT-191 in Fabry disease is a significant milestone for uniQure. This gene therapy candidate leverages the company's proven AAV5 delivery technology, which has shown success with HEMGENIX®. The trial's design, focusing on safety, tolerability and early efficacy signals, is important for establishing AMT-191's potential.
Key points to consider:
- The trial's two-cohort structure allows for dose optimization
- Utilization of established Fabry disease endpoints may accelerate proof-of-concept
- AMT-191's liver-targeting approach could offer a differentiated profile in the Fabry treatment landscape
While promising, investors should note that this is an early-stage trial and significant hurdles remain before potential commercialization.
uniQure's advancement of AMT-191 into clinical trials demonstrates the company's pipeline expansion and potential for future revenue streams. Key financial implications include:
- Extended cash runway through
2027 , providing ample time for clinical development - Potential for value creation through multiple catalysts across the pipeline
- Diversification of risk by advancing multiple programs simultaneously
However, investors should be aware that clinical-stage biotech companies often face significant cash burn. The success of AMT-191 and other pipeline candidates will be important for uniQure's long-term financial health and stock performance. The company's cost reduction initiatives are a positive sign of financial prudence during this critical development phase.
LEXINGTON, Mass. and AMSTERDAM, Aug. 15, 2024 (GLOBE NEWSWIRE) -- uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced that the first patient has been dosed in a Phase I/IIa clinical trial of AMT-191 for the treatment of Fabry disease, a rare, inherited genetic disease. The Phase I/IIa study is a multi-center, open-label trial being conducted in the United States with two dose-escalating cohorts assessing the safety, tolerability and early signs of efficacy of AMT-191 in individuals with Fabry disease.
“We are very pleased to begin patient dosing for AMT-191 in Fabry disease, marking a significant milestone in this year’s goal to advance three new gene therapy candidates into clinical studies,” stated Walid Abi-Saab, M.D., chief medical officer of uniQure. “AMT-191 utilizes the same AAV delivery technology incorporated in HEMGENIX®, which has an extensive, long-term safety profile and demonstrated effectiveness in patients with preexisting neutralizing antibodies to the AAV capsid. Our trial is designed to capture well-established endpoints in Fabry disease and to rapidly generate clinical proof-of-concept data for AMT-191 with a differentiated product profile relative to other Fabry programs in clinical development.”
AMT-191 is an investigational AAV5-based gene therapy that uses a proprietary, highly potent promoter to deliver a galactosidase alpha (GLA) transgene designed to target the liver to produce GLA protein. In patients with Fabry disease, a pathogenic variant in the GLA gene leads to α-galactosidase A (aGAL-A) enzyme deficiency, which in turn results in a progressive accumulation of lipids in multiple cell types, including kidney and heart cells, eventually resulting in a multi-system disorder. AMT-191 may offer a novel potential one-time intravenously administered approach to treating Fabry disease.
The Phase I/IIa clinical trial of AMT-191 will be conducted in the United States. The multicenter, open-label trial consists of two cohorts with up to six adult male patients each: a low-dose cohort of 6x1013 gc/kg and a high-dose cohort of 3x1014 gc/kg delivered through a one-time intravenous infusion. Patients will continue to receive their regular enzyme replacement therapy until the criteria for withdrawal is met and will be followed for a period of 24 months. The trial will explore the safety, tolerability, and early signs of efficacy by measuring the expression of lysosomal enzyme aGLA-A. Additional details are available on www.clinicaltrials.gov (NCT06270316).
“This achievement marks an exciting period for the company as we advance additional programs into clinical trials this year,” stated Matt Kapusta, chief executive officer of uniQure. “Building on our momentum, we are focused on multiple, exciting catalysts across our pipeline, including engaging with the FDA to pursue an expedited clinical pathway for AMT-130 in Huntington’s disease and the initiation of new clinical studies in temporal lobe epilepsy and SOD1-ALS. With a strong balance sheet and runway extended through the end of 2027 from multiple cost reduction initiatives, we believe we are in an excellent position to execute on key value-creating milestones.”
About Fabry Disease
Fabry disease is an Xlinked- genetic disorder resulting from a deficiency of GLA. Based on a 2020 study published in the Journal of Therapeutics and Clinical Risk Management, the prevalence is estimated to be between one in 40,000 and one in 117,000 individuals. The current standard of care for Fabry disease is bi-weekly infusions of enzyme replacement therapy, a treatment with limited effectiveness in many patients due to poor cross-correction, with inefficient clearance of substrates in the target organs, in particular the kidney and the heart.
About uniQure
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. 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. 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 regarding the timing of patient dosing and the availability of initial clinical and proof-of-concept data in the Company’s open-label U.S. Phase I/IIa trial for Fabry disease; the trial design and the differentiated profile of AMT-191 relative to other Fabry programs currently in clinical development. The Company’s actual results could differ materially from those anticipated in these forward-looking statements for many reasons. These risks and uncertainties include, without limitation, risks associated with the clinical results and the development and timing of the Company’s programs; the Company’s interactions with regulatory authorities, which may affect the initiation, timing and progress of clinical trials and pathways to approval; risks associated with the implementation of the Company’s restructuring plans; the Company’s ability to continue to build and maintain the company infrastructure and personnel needed to achieve its goals following planned workforce reductions; the Company’s effectiveness in managing current and future clinical trials and regulatory processes; the continued development and acceptance of gene therapies; the Company’s ability to demonstrate the therapeutic benefits of its gene therapy candidates in clinical trials; the Company’s ability to obtain, maintain and protect intellectual property; and the Company’s ability to fund its operations and to raise additional capital as needed. These risks and uncertainties are more fully described under the heading "Risk Factors" in the Company’s periodic filings with the U.S. Securities & Exchange Commission (“SEC”), including its Annual Report on Form 10-K filed February 28, 2024, its Quarterly Reports on Form 10-Q filed May 7, 2024 and August 1, 2024, 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 the Company assumes no obligation to update these forward-looking statements, even if new information becomes available in the future.
uniQure Contacts:
| FOR INVESTORS: | FOR MEDIA: | |
| Chiara Russo | Tom Malone | |
| Direct: 617-306-9137 | Direct: 339-970-7558 | |
| Mobile: 617-306-9137 | Mobile:339-223-8541 | |
| c.russo@uniQure.com | t.malone@uniQure.com | |
FAQ
What is the purpose of uniQure's AMT-191 Phase I/IIa clinical trial?
How many patients will be enrolled in uniQure's AMT-191 trial for Fabry disease?
What is the dosing regimen for AMT-191 in uniQure's Fabry disease trial?
How long will patients be followed in uniQure's AMT-191 trial for Fabry disease?
What other clinical programs is uniQure (QURE) advancing in 2024?
