uniQure Announces Initial AMT-191 Phase I/IIa Data Showing Sustained Increases in α-Gal A Enzyme Activity in Patients with Fabry Disease
uniQure (NASDAQ: QURE) has announced promising initial data from its Phase I/IIa trial of AMT-191, a gene therapy for Fabry disease. The first cohort of four patients demonstrated remarkable results, with α-Gal A enzyme activity increasing 27- to 208-fold above normal levels.
All patients in Cohort A (6x1013 gc/kg) successfully discontinued enzyme replacement therapy (ERT) while maintaining stable plasma lyso-Gb3 levels. The therapy showed a manageable safety profile, though some adverse events were reported. A second cohort with a lower dose (2x1013 gc/kg) has completed enrollment with no serious adverse events reported to date.
The company plans to present updated clinical results in the first half of 2026.
uniQure (NASDAQ: QURE) ha annunciato dati iniziali promettenti dal suo studio di fase I/IIa su AMT-191, una terapia genica per la malattia di Fabry. Il primo gruppo di quattro pazienti ha mostrato risultati notevoli, con l'attività dell'enzima α-Gal A aumentata da 27 a 208 volte rispetto ai livelli normali.
Tutti i pazienti del Cohort A (6x1013 gc/kg) hanno interrotto con successo la terapia enzimatica sostitutiva (ERT) mantenendo stabili i livelli plasmatici di lyso-Gb3. La terapia ha evidenziato un profilo di sicurezza gestibile, sebbene siano stati riportati alcuni eventi avversi. Un secondo gruppo con dose più bassa (2x1013 gc/kg) ha completato l'arruolamento senza che siano stati riportati finora eventi avversi gravi.
La società prevede di presentare risultati clinici aggiornati nella prima metà del 2026.
uniQure (NASDAQ: QURE) ha anunciado datos iniciales prometedores de su ensayo de fase I/IIa de AMT-191, una terapia génica para la enfermedad de Fabry. La primera cohorte de cuatro pacientes mostró resultados destacados, con la actividad de la enzima α-Gal A aumentando entre 27 y 208 veces por encima de los niveles normales.
Todos los pacientes de la Cohorte A (6x1013 gc/kg) dejaron con éxito la terapia de reemplazo enzimático (ERT) manteniendo niveles plasmáticos estables de lyso-Gb3. La terapia presentó un perfil de seguridad manejable, aunque se informaron algunos eventos adversos. Una segunda cohorte con una dosis menor (2x1013 gc/kg) completó el reclutamiento sin que se hayan reportado hasta la fecha eventos adversos graves.
La compañía planea presentar resultados clínicos actualizados en la primera mitad de 2026.
uniQure (NASDAQ: QURE)는 파브리병 치료용 유전자치료제 AMT-191의 임상 1/2a상 초기 유망한 데이터를 발표했습니다. 첫 번째 코호트의 네 명 환자에서 뛰어난 결과가 나타났으며, α-Gal A 효소 활성은 정상 수치보다 27배에서 208배까지 증가했습니다.
Cohort A(6x1013 gc/kg)의 모든 환자는 효소 대체 요법(ERT)을 성공적으로 중단하면서 혈장 lyso-Gb3 수치를 안정적으로 유지했습니다. 치료는 관리 가능한 안전성 프로파일을 보였지만 일부 이상반응이 보고되었습니다. 더 낮은 용량(2x1013 gc/kg)의 두 번째 코호트는 등록을 완료했으며 현재까지 중대한 이상반응은 보고되지 않았습니다.
회사는 2026년 상반기에 업데이트된 임상 결과를 발표할 계획입니다.
uniQure (NASDAQ: QURE) a annoncé des données initiales prometteuses de son essai de phase I/IIa sur AMT-191, une thérapie génique pour la maladie de Fabry. La première cohorte de quatre patients a montré des résultats remarquables, avec une activité enzymatique α-Gal A augmentée de 27 à 208 fois par rapport aux niveaux normaux.
Tous les patients de la cohorte A (6x1013 gc/kg) ont arrêté avec succès la thérapie de remplacement enzymatique (ERT) tout en maintenant des taux plasmatiques de lyso-Gb3 stables. La thérapie a présenté un profil d'innocuité gérable, bien que certains événements indésirables aient été signalés. Une seconde cohorte avec une dose plus faible (2x1013 gc/kg) a terminé le recrutement et aucun événement indésirable grave n'a été signalé à ce jour.
La société prévoit de présenter des résultats cliniques mis à jour au cours de la première moitié de 2026.
uniQure (NASDAQ: QURE) hat vielversprechende Anfangsdaten aus seiner Phase-I/IIa-Studie zu AMT-191, einer Gentherapie für die Fabry-Krankheit, bekannt gegeben. Die erste Kohorte mit vier Patienten zeigte bemerkenswerte Ergebnisse, wobei die α-Gal A-Enzymaktivität um das 27- bis 208-Fache über dem Normalwert anstieg.
Alle Patienten in Kohorte A (6x1013 gc/kg) konnten die Enzymersatztherapie (ERT) erfolgreich absetzen und behielten stabile Plasmalevels von lyso-Gb3. Die Therapie zeigte ein handhabbares Sicherheitsprofil, wenngleich einige unerwünschte Ereignisse berichtet wurden. Eine zweite Kohorte mit niedrigerer Dosis (2x1013 gc/kg) hat die Einschreibung abgeschlossen, ohne dass bislang schwerwiegende unerwünschte Ereignisse gemeldet wurden.
Das Unternehmen plant, aktualisierte klinische Ergebnisse in der ersten Hälfte von 2026 vorzustellen.
- All patients achieved 27-208 fold increases in α-Gal A enzyme activity above normal levels
- All patients successfully discontinued enzyme replacement therapy (ERT)
- Sustained elevated enzyme levels observed for up to 45 weeks post-treatment
- Lower dose cohort shows no serious adverse events to date
- Five serious adverse events (SAEs) reported in two patients in the high-dose cohort
- One patient experienced Grade 3 liver enzyme elevation requiring corticosteroid therapy
- One dose-limiting toxicity observed in the high-dose cohort
Insights
uniQure's AMT-191 gene therapy for Fabry disease shows remarkable early efficacy with manageable safety profile, potentially eliminating need for lifelong enzyme treatments.
uniQure's Phase I/IIa trial for AMT-191 presents highly encouraging preliminary results in the treatment of Fabry disease. The first cohort receiving the higher dose (6x1013 gc/kg) demonstrated extraordinary enzyme activity increases ranging from 27- to 208-fold above normal levels, sustained for up to 45 weeks post-treatment. This supraphysiological expression represents a significant breakthrough, as the current standard treatments only temporarily elevate enzyme levels.
The ability of all four patients to discontinue enzyme replacement therapy (ERT) while maintaining stable lyso-Gb3 levels is particularly noteworthy. Current Fabry disease management typically requires biweekly ERT infusions throughout a patient's life, representing a substantial treatment burden and cost. A one-time gene therapy eliminating this need would be transformative.
The safety profile appears generally manageable, though not without concerns. The observation of two treatment-related SAEs (chest pain, increased troponin) and one possibly related SAE (leptomeningeal enhancement) warrant close monitoring. The Grade 3 liver enzyme elevation, while resolved with corticosteroids, is a known challenge with AAV vector-based gene therapies.
The initiation of a lower-dose cohort (2x1013 gc/kg) with no SAEs reported to date suggests uniQure is appropriately exploring the therapeutic window. The AAV5 vector with proprietary promoter appears to successfully deliver sustained enzyme expression, addressing the fundamental metabolic defect in Fabry disease. If these results are maintained long-term, AMT-191 could potentially provide a functional cure for this progressive and debilitating lysosomal storage disorder.
~ All patients in the first cohort achieved between 27- to 208-fold increases in α-Gal A activity relative to mean normal level ~
~ All patients in first cohort discontinued enzyme replacement therapy ~
~ Preliminary data show AMT-191 has a manageable safety profile at the highest dose ~
~ Updated clinical results expected in the first half of 2026 ~
LEXINGTON, Mass. and AMSTERDAM, Sept. 05, 2025 (GLOBE NEWSWIRE) -- uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced initial safety and exploratory efficacy data from the first cohort of its Phase I/IIa trial of AMT-191, an investigational gene therapy for the treatment of Fabry disease. The preliminary data were presented at the International Congress of Inborn Errors of Metabolism (ICIEM) in Kyoto, Japan.
Fabry disease is a genetic lysosomal storage disorder caused by a deficiency of the α-galactosidase A (α-Gal A) enzyme, leading to toxic accumulation of globotriaosylsphingosine (lyso-Gb3) that can damage the kidneys, heart, nervous system, eyes, gut and skin. AMT-191 is designed as a one-time, intravenously administered, investigational AAV5-based gene therapy that incorporates a proprietary, highly potent promoter designed to achieve supraphysiological α-Gal A expression.
As of the July 24, 2025 study cutoff date, all four patients in the first cohort, Cohort A (6x1013 genome copies/kilogram (gc/kg)), showed substantial increases in α-Gal A activity, ranging from 27- to 208-fold above the mean normal level1. Sustained elevated levels were observed in all four patients in the first cohort as of the study cutoff date, which was as long as 45 weeks post-treatment for the first treated patient and 12 weeks post-treatment for the most recently treated patient. All four patients were withdrawn from enzyme replacement therapy (ERT) and maintained stable plasma lyso-Gb3 levels through the cutoff date.
“These initial findings from the first cohort are encouraging, with all patients showing robust increases in α-Gal A activity and an ability to withdraw from ERT,” stated Walid Abi-Saab, M.D., chief medical officer of uniQure. “The early data highlight the potential of AMT-191 as a transformative one-time treatment option for people living with Fabry disease. I look forward to sharing additional data from our dose-finding study expected in the first half of 2026.”
Based on data observed to date, AMT-191 showed a manageable safety profile. At the 6x1013 gc/kg dose, two Serious Adverse Events (SAEs) unrelated to AMT-191 (stroke, diplopia), two related SAEs (chest pain, increased troponin), and one possibly related SAE (leptomeningeal enhancement) were observed in two patients. Additionally, one patient experienced an asymptomatic Grade 3 liver enzyme elevation that resolved with corticosteroid therapy. This event, classified as a dose-limiting toxicity per protocol, was not considered serious and did not require hospitalization. No loss of α-Gal A expression was observed in this patient.
Enrollment was completed in a second, lower dose cohort, Cohort B (2x1013 gc/kg), consisting of three patients. As of the study cutoff date, all patients had less than three months of follow-up. To date, no SAEs were reported in the second cohort. uniQure expects to present updated results from the Phase I/IIa clinical trial in the first half of 2026.
About the Phase I/IIa Clinical Program of AMT-191
The Phase I/IIa clinical trial of AMT-191 is a multi-center, open-label trial being conducted in the United States consisting of three dosing cohorts of three or more adult male patients each receiving an intravenous infusion of AMT-191. Patients were not excluded from the trial based on pre-existing neutralizing anti-bodies to AAV5. Patients continue to receive their regular enzyme replacement therapy until meeting withdrawal criteria 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 α-Gal A. Additional details are available on www.clinicaltrials.gov (NCT06270316).
AMT-191 has been granted both Orphan Drug and Fast Track designation by the U.S. Food and Drug Administration.
About Fabry Disease
Fabry disease is an X-linked 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 potential of AMT-191 as a transformative one-time intravenously administered option for treating Fabry disease and the Company’s plans to present updated Phase I/IIa clinical trial data for AMT-191 in the first half of 2026. 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 and timing for regulatory approval; the Company’s ability to continue to build and maintain the company infrastructure and personnel needed to achieve its goals; 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 with the SEC on February 27, 2025, its Quarterly Reports on Form 10-Q filed with the SEC on May 9, 2025 and July 29, 2025, 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: 781-491-4371 | Direct: 339-970-7558 |
| Mobile: 617-306-9137 | Mobile:339-223-8541 |
| c.russo@uniQure.com | t.malone@uniQure.com |
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1 Normal range (1.38 – 8.66 nmol); mean normal of 3.57 nmol
FAQ
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