uniQure Announces Dosing of First Patient in GenTLE Phase I/IIa Clinical Trial of AMT-260 for the Treatment of Refractory Mesial Temporal Lobe Epilepsy
uniQure has announced the dosing of the first patient in its GenTLE Phase I/IIa clinical trial of AMT-260, targeting refractory mesial temporal lobe epilepsy (MTLE). The trial evaluates a one-time gene therapy treatment using an AAV9 vector that delivers engineered miRNAs to reduce GluK2 protein expression, which is believed to trigger seizures in MTLE patients. The study will include two dose cohorts of six patients each across 10 active sites, with two additional sites planned by end of 2024. Preclinical studies showed AMT-260 reduced seizure frequency in a dose-dependent manner and decreased GluK2 expression in both animal models and patient tissue samples.
uniQure ha annunciato la somministrazione del primo paziente nel suo trial clinico GenTLE di Fase I/IIa per AMT-260, mirato all'epilessia mesiale temporale refrattaria (MTLE). Lo studio valuta un trattamento di terapia genica effettuato una sola volta utilizzando un vettore AAV9 che consegna miRNA ingegnerizzati per ridurre l'espressione della proteina GluK2, ritenuta responsabile delle crisi nei pazienti affetti da MTLE. Lo studio prevede due coorti di dosaggio di sei pazienti ciascuna distribuite su 10 siti attivi, con due siti aggiuntivi previsti per la fine del 2024. Studi preclinici hanno dimostrato che AMT-260 riduce la frequenza delle crisi in modo dose-dipendente e diminuisce l'espressione di GluK2 sia in modelli animali che in campioni di tessuto dei pazienti.
uniQure ha anunciado la dosificación del primer paciente en su ensayo clínico GenTLE de Fase I/IIa de AMT-260, dirigido a la epilepsia mesial del lóbulo temporal refractaria (MTLE). El ensayo evalúa un tratamiento de terapia génica de una sola vez usando un vector AAV9 que entrega miARNs diseñados para reducir la expresión de la proteína GluK2, que se cree que desencadena convulsiones en pacientes con MTLE. El estudio incluirá dos cohortes de dosis de seis pacientes cada una en 10 sitios activos, con dos sitios adicionales planeados para finales de 2024. Los estudios preclínicos mostraron que AMT-260 redujo la frecuencia de las convulsiones de manera dependiente de la dosis y disminuyó la expresión de GluK2 tanto en modelos animales como en muestras de tejido de pacientes.
uniQure는 AMT-260의 GenTLE Phase I/IIa 임상 시험에서 첫 환자의 용량 투여를 발표했습니다. 이 시험은 내성 측두엽 간질(MTLE)을 목표로 하고 있습니다. 연구는 AAV9 벡터를 사용하여 설계된 miRNA를 전달하고 GluK2 단백질 발현을 줄여 MTLE 환자의 발작을 유발하는 것으로 알려진 치료제를 단 한 번 투여하는 유전자 치료법을 평가합니다. 이 연구는 10개의 활성 사이트에서 각각 여섯 명의 환자로 구성된 두 개의 용량 집단을 포함할 예정이며, 2024년 말까지 두 개의 추가 사이트가 계획되어 있습니다. 전임상 연구에서는 AMT-260이 용량 의존적인 방식으로 발작 빈도를 줄이고, 동물 모델 및 환자 조직 샘플에서 GluK2 발현을 감소시켰음을 보여주었습니다.
uniQure a annoncé la dose du premier patient dans son essai clinique GenTLE de Phase I/IIa d'AMT-260, ciblant l'épilepsie temporale mesiale réfractaire (MTLE). L'essai évalue un traitement de thérapie génique administré une seule fois utilisant un vecteur AAV9 qui délivre des miARNs conçus pour réduire l'expression de la protéine GluK2, que l'on pense être à l'origine des crises chez les patients atteints de MTLE. L'étude comprendra deux cohortes de dose de six patients chacune à travers 10 sites actifs, avec deux sites supplémentaires prévus d'ici la fin de 2024. Les études précliniques ont montré qu'AMT-260 réduisait la fréquence des crises de manière dépendante à la dose et diminuait l'expression de GluK2 tant dans des modèles animaux que dans des échantillons de tissus de patients.
uniQure hat die Dosierung des ersten Patienten in seiner GenTLE Phase I/IIa-Studie zu AMT-260 angekündigt, die auf refraktäre mesiale Temporallappenepilepsie (MTLE) abzielt. Die Studie bewertet eine einmalige Gentherapie-Behandlung mit einem AAV9-Vektor, der gentechnisch veränderte miRNAs liefert, um die Expression des GluK2-Proteins zu reduzieren, das als Auslöser von Anfällen bei MTLE-Patienten angesehen wird. Die Studie umfasst zwei Dosierungsgruppen mit jeweils sechs Patienten an 10 aktiven Standorten, wobei bis Ende 2024 zwei weitere Standorte geplant sind. Präklinische Studien zeigten, dass AMT-260 die Anfallshäufigkeit dosisabhängig reduzierte und sowohl in Tiermodellen als auch in Gewebeproben von Patienten die GluK2-Expression senkte.
- First patient dosed in Phase I/IIa trial represents third clinical trial initiation in six months
- Preclinical studies demonstrated dose-dependent reduction in seizures
- Treatment addresses unmet need for one-third of patients not responding to current treatments
- Early-stage trial with efficacy yet to be proven in humans
- patient enrollment with only 12 patients planned for the study
Insights
The initiation of the GenTLE Phase I/IIa trial for AMT-260 represents a significant milestone in addressing the unmet needs of refractory MTLE patients. The trial's innovative approach using AAV9 vector delivery of engineered miRNAs targeting GluK2 protein expression shows promise based on preclinical data. However, investors should note several key considerations:
Key Points:
- This is an early-stage trial with 12 patients across two dose cohorts, indicating results are still years away
- The addressable market includes
30% of focal onset seizure patients who don't respond to current treatments - The one-time administration model aligns with successful gene therapy approaches
- Preclinical data showing dose-dependent seizure reduction provides encouraging proof-of-concept
While this development expands uniQure's clinical pipeline, the small market cap suggests investors are taking a cautious stance on the company's overall prospects. Near-term catalysts will be to safety data and initial efficacy signals.
LEXINGTON, Mass. and AMSTERDAM, Nov. 21, 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 the GenTLE Phase I/IIa clinical trial of AMT-260 for the treatment of refractory mesial temporal lobe epilepsy (MTLE).
“The dosing of the first patient in our Phase I/II trial in temporal lobe epilepsy represents an important milestone for uniQure and our third clinical trial initiation over the past six months,” stated Walid Abi-Saab, M.D., chief medical officer of uniQure. “Nearly one-third of people experiencing focal onset seizures do not respond to currently available treatments and are left with limited therapeutic options. Our investigational agent, AMT-260, which is a one-time administration, has the potential to be a transformative treatment option for these patients. We continue to actively screen patients for the trial and look forward to providing program updates in the new year.”
AMT-260 consists of an AAV9 vector that locally delivers two engineered miRNAs designed to reduce the expression of GluK2 protein subunits, a subtype of glutamate receptor that is believed to be aberrantly expressed in the hippocampus of patients with refractory MTLE and believed to trigger their seizure activity. In preclinical animal studies, AMT-260 reduced the number of seizures per day in a dose-dependent manner. AMT-260 also reduced the expression of GluK2 mRNA and protein in the hippocampus of epileptic mice and from resected hippocampal slices from patients with refractory MTLE.
GenTLE is a Phase I/IIa multi-center, open-label trial being conducted in the U.S. to evaluate the safety, tolerability and exploratory signs of efficacy of two doses of AMT-260 in individuals with refractory MTLE. The study comprises two dose cohorts of six patients each. The study is actively recruiting though 10 sites with an additional two sites expected to be activated by the end of 2024. Additional details are available on www.clinicaltrials.gov (NCT06063850).
About Refractory Mesial Temporal Lobe Epilepsy
Temporal lobe epilepsy is a chronic neurologic disorder and is the most common form of focal epilepsy with more than 600,000 individuals suffering from the disorder in the United States. Approximately
About uniQure
uniQure’s mission is to reimagine the future of medicine by delivering innovative cures that transform lives. The recent approvals of our gene therapy for hemophilia B – a 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. We are now leveraging our modular and validated technology and manufacturing platform to advance a pipeline of proprietary gene therapies for the treatment of patients with Huntington's disease, refractory mesial temporal lobe epilepsy, amyotrophic lateral sclerosis (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 AMT-260’s potential to be a transformative treatment option for these patients with MTLE; the potential efficacy profile of AMT-260 through one-time administration with the ability to reduce the frequency of seizures in MTLE patients; the Company’s plans to announce additional updates on trial enrollment; the design of the AMT-260 Phase I/IIa clinical trial and plans to activate additional study sites. 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; 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 February 28, 2024, its Quarterly Reports on Form 10-Q filed May 7, 2024, August 1, 2024 and November 5, 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
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