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uniQure Announces Alignment with FDA on Key Elements of Accelerated Approval Pathway for AMT-130 in Huntington’s Disease

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uniQure has reached an agreement with the FDA on key elements for an Accelerated Approval pathway for AMT-130, their Huntington's disease treatment. The FDA agreed that data from ongoing Phase I/II studies compared to natural history external control can serve as the primary basis for a Biologics License Application (BLA), eliminating the need for additional pre-submission studies.

The FDA accepted the composite Unified Huntington's Disease Rating Scale (cUHDRS) as an intermediate clinical endpoint and acknowledged that reductions in neurofilament light chain (NfL) in cerebrospinal fluid may support evidence of therapeutic benefit. This follows the RMAT designation granted in May 2024 and promising interim data from July 2024 showing durable, dose-dependent slowing of disease progression.

uniQure ha raggiunto un accordo con la FDA su elementi chiave per un percorso di approvazione accelerata per AMT-130, il loro trattamento per la malattia di Huntington. La FDA ha concordato che i dati degli studi Fase I/II in corso, confrontati con un controllo esterno basato sulla storia naturale, possono costituire la base principale per una richiesta di licenza biologica (BLA), eliminando la necessità di ulteriori studi pre-invio.

La FDA ha accettato la scala composita Unificata di Valutazione della Malattia di Huntington (cUHDRS) come un endpoint clinico intermedio e ha riconosciuto che le riduzioni della catena leggera di neurofilamento (NfL) nel liquido cerebrospinale possono supportare le prove di beneficio terapeutico. Questo segue la designazione RMAT concessa a maggio 2024 e i promettenti dati intermedi di luglio 2024 che mostrano un rallentamento duraturo e dose-dipendente della progressione della malattia.

uniQure ha llegado a un acuerdo con la FDA sobre elementos clave para una vía de Aprobación Acelerada para AMT-130, su tratamiento para la enfermedad de Huntington. La FDA acordó que los datos de los estudios en Fase I/II en curso, en comparación con un control externo basado en la historia natural, pueden servir como base principal para una Solicitud de Licencia Biológica (BLA), eliminando la necesidad de estudios adicionales antes de la presentación.

La FDA aceptó la escala compuesta Unificada de Evaluación de la Enfermedad de Huntington (cUHDRS) como un punto final clínico intermedio y reconoció que las reducciones en la cadena ligera de neurofilamento (NfL) en el líquido cefalorraquídeo pueden respaldar evidencia de beneficio terapéutico. Esto sigue la designación RMAT otorgada en mayo de 2024 y datos interinos prometedores de julio de 2024 que muestran un desaceleramiento duradero y dependiente de la dosis de la progresión de la enfermedad.

uniQureAMT-130에 대한 가속 승인 경로의 주요 요소에 대해 FDA와 합의에 도달했습니다. 이는 헌팅턴병 치료제입니다. FDA는 현재 진행 중인 1/2상 연구의 데이터가 자연사 외부 대조군과 비교되어 생물학적 제품 허가 신청(BLA)의 기본 근거로 사용할 수 있다고 동의했습니다. 이는 추가적인 제출 전 연구의 필요성을 없애줍니다.

FDA는 통합 헌팅턴병 평가 척도(cUHDRS)를 중간 임상 지표로 수용했으며, 뇌척수액 내 신경 필라멘트 경량 체인(NfL)의 감소가 치료적 이점의 증거를 뒷받침할 수 있음을 인정했습니다. 이는 2024년 5월에 부여된 RMAT 지정과 2024년 7월의 유망한 중간 데이터를 따른 결과로, 이는 질병 진행의 지속적이고 용량 의존적인 완화를 보여줍니다.

uniQure a conclu un accord avec la FDA sur des éléments clés pour un parcours d'approbation accélérée pour AMT-130, leur traitement de la maladie de Huntington. La FDA a convenu que les données des études de Phase I/II en cours, comparées à un contrôle externe basé sur l'histoire naturelle, peuvent servir de base principale pour une demande de licence biologique (BLA), éliminant ainsi le besoin d'études supplémentaires avant la soumission.

La FDA a accepté l'échelle unifiée composite d'évaluation de la maladie de Huntington (cUHDRS) comme un critère d'évaluation clinique intermédiaire et a reconnu que les réductions de la chaîne légère de neurofilament (NfL) dans le liquide céphalorachidien peuvent soutenir des preuves de bénéfice thérapeutique. Cela fait suite à la désignation RMAT accordée en mai 2024 et aux données intermédiaires prometteuses fournies en juillet 2024 montrant un ralentissement durable et dépendant de la dose de la progression de la maladie.

uniQure hat eine Vereinbarung mit der FDA über zentrale Elemente für einen beschleunigten Genehmigungsweg für AMT-130, ihre Behandlung der Huntington-Krankheit, erreicht. Die FDA stimmte zu, dass die Daten aus den laufenden Phase-I/II-Studien im Vergleich zu einem externen Kontrollstandard der natürlichen Krankheitsgeschichte als primäre Grundlage für einen Antrag auf biologische Lizenz (BLA) dienen können, wodurch die Notwendigkeit zusätzlicher Vorantragsstudien entfällt.

Die FDA akzeptierte die zusammengesetzte einheitliche Bewertungsskala für die Huntington-Krankheit (cUHDRS) als intermediäres klinisches Endziel und erkannte an, dass die Reduzierung der leichten Ketten von Neurofilamenten (NfL) in der Gehirn-Rückenmarks-Flüssigkeit Beweise für therapeutischen Nutzen unterstützen kann. Dies folgt der im Mai 2024 gewährten RMAT-Bestimmung und vielversprechenden vorläufigen Daten aus Juli 2024, die eine nachhaltige, dosisabhängige Verlangsamung des Krankheitsverlaufs zeigen.

Positive
  • FDA agreement eliminates need for additional pre-submission studies, potentially accelerating time to market
  • Received RMAT designation in May 2024, indicating potential to address unmet medical needs
  • Interim data shows dose-dependent slowing of disease progression at 24 months
  • Demonstrated reductions in CSF NfL, indicating reduced neurodegeneration
Negative
  • Product still in Phase I/II stage, requiring completion of trials and full approval process
  • Accelerated approval pathway still requires post-approval confirmatory evidence

Insights

The FDA's agreement on an Accelerated Approval pathway for AMT-130 marks a significant regulatory milestone for uniQure's Huntington's disease gene therapy. The acceptance of Phase I/II data with natural history controls eliminates the need for additional pre-submission studies, potentially reducing development time and costs by years.

The validation of cUHDRS as an intermediate clinical endpoint, supported by NfL biomarker data, strengthens the regulatory package. The 24-month interim data showing dose-dependent disease progression slowing and reduced neurodegeneration markers provides compelling evidence for therapeutic efficacy. This regulatory alignment substantially de-risks the approval pathway and could accelerate market access for this first-in-class treatment.

This regulatory breakthrough could significantly enhance uniQure's market position in the $14 billion Huntington's disease therapeutics market. The Accelerated Approval pathway typically reduces time-to-market by 2-4 years, providing a important competitive advantage in the race to develop effective treatments for this devastating condition.

The RMAT designation and FDA's collaborative stance suggest strong commercial potential for AMT-130. With no disease-modifying treatments currently available for Huntington's disease, AMT-130 could capture substantial market share if approved. This development should positively impact uniQure's valuation metrics and investor confidence, particularly given the company's current market cap of $347 million.

~ U.S. Food and Drug Administration (FDA) agrees that data from ongoing Phase I/II studies compared to a natural history external control may serve as the primary basis for a Biologics License Application (BLA) for Accelerated Approval ~

~ FDA agrees that the composite Unified Huntington’s Disease Rating Scale (cUHDRS) may serve as an intermediate clinical endpoint for Accelerated Approval ~        

~ Conference call today at 8:30 a.m. ET ~

LEXINGTON, Mass. and AMSTERDAM, Dec. 10, 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 company reached agreement with the U.S. Food and Drug Administration (FDA) on key elements of an Accelerated Approval pathway for AMT-130.

“We are very pleased to reach agreement with the FDA on core components of an Accelerated Approval pathway for AMT-130,” said Walid Abi-Saab, M.D., chief medical officer of uniQure. “Our alignment reflects the strength of our data and collaborative discussions with the staff and senior management at FDA’s Center for Biologics Evaluation and Research (CBER). This is an important milestone for the Huntington’s disease community as it puts us on the most rapid and efficient pathway to deliver a potentially life-changing therapy to people living with this devastating neurodegenerative disorder. 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, avoiding the need for an additional pre-submission study. 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.

The FDA granted uniQure RMAT designation for AMT-130 in May 2024, stating that preliminary clinical data from the ongoing Phase I/II studies indicate AMT-130 has the potential to address unmet medical needs for the treatment of Huntington’s disease. In July 2024, uniQure presented interim data at 24 months showing durable, dose-dependent slowing of disease progression based on the cUHDRS of treated patients compared to a propensity-weighted natural history. These data also showed reductions in CSF NfL, a measure of neurodegeneration, in treated patients at 24 months compared to baseline.

Investor Conference Call and Webcast Information

uniQure management will host an investor conference call and webcast today, Tuesday, December 10 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 is enrolling an additional 12 patients across sites in the U.S. and EU. This cohort is randomized to explore both doses of AMT-130 in combination with immunosuppression, using the current, established stereotactic administration procedure.  

Additional details are available on www.clinicaltrials.gov (NCT0543017, NCT04120493)

AMT-130 was granted the FDA’s Regenerative Medicine Advanced Therapy (RMAT) designation, the first for Huntington’s disease.

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.

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 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 plans to initiate BLA-readiness activities; 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 Company’s plans for further engagement with the FDA in the first half of 2025; the potential clinical and functional effects of AMT-130; the Company’s plans to continue clinical development of AMT-130; the Company’s enrollment plans with respect to the third cohort of the Phase I/II study; and the utility of NfL in CSF as an effective biomarker of therapeutic benefit. The Company’s actual results could differ materially from those anticipated in these forward-looking statements for many reasons. These risks and uncertainties include, among others: risks related to the Company’s Phase I/ll clinical trials of AMT-130, including the risk that interim data from the trials may not be predictive of later data readouts that will serve as a basis for further regulatory interactions; risks related to the Company’s current and future interactions with regulatory authorities, which may affect the initiation, timing and progress of clinical trials, its BLA submission plans and pathways to regulatory approval; risks related to the Company’s ability to pursue business development efforts with respect to AMT-130;risks related to the Company’s use of propensity-weighted external controls in connection with its statistical analysis of clinical outcomes to date, and whether regulatory authorities will accept the Company’s approach as a basis for accelerated approval; risks related to the Company’s use of nominal p values as a basis for its statistical analyses; whether the measurements that the Company is evaluating continue to be viewed as robust and sensitive measurements of disease progression; whether RMAT designation or any accelerated pathway, will lead to regulatory approval; the Company’s ability to continue to build and maintain the infrastructure and personnel needed to achieve its goals; the Company’s effectiveness in managing current and future clinical trials and regulatory processes; the Company’s ability to demonstrate the therapeutic benefits of its gene therapy candidates in clinical trials; the continued development and acceptance of gene therapies; the Company’s ability to obtain, maintain and protect its intellectual property; and the Company’s ability to fund its operations and to raise additional capital as needed and on acceptable terms. 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 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, except as required by law, 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: 617-306-9137Direct: 339-970-7558
Mobile: 617-306-9137Mobile:339-223-8541
c.russo@uniQure.comt.malone@uniQure.com

FAQ

What did the FDA agree to regarding uniQure's AMT-130 approval pathway?

The FDA agreed that Phase I/II study data compared to natural history external control can serve as primary basis for BLA submission, and that cUHDRS can be used as an intermediate clinical endpoint for Accelerated Approval.

What were the key findings from uniQure's (QURE) AMT-130 interim data in July 2024?

The interim data showed durable, dose-dependent slowing of disease progression based on cUHDRS compared to natural history, and reductions in CSF NfL at 24 months compared to baseline.

When did uniQure (QURE) receive RMAT designation for AMT-130?

uniQure received RMAT designation for AMT-130 in May 2024, based on preliminary clinical data showing potential to address unmet medical needs in Huntington's disease treatment.

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