Ultragenyx Announces FDA Acceptance and Priority Review of the Biologics License Application (BLA) for UX111 AAV Gene Therapy to Treat Sanfilippo Syndrome Type A (MPS IIIA)
Ultragenyx Pharmaceutical (NASDAQ: RARE) announced FDA acceptance of their Biologics License Application (BLA) for UX111, an AAV gene therapy targeting Sanfilippo syndrome type A (MPS IIIA). The FDA granted Priority Review with a PDUFA date of August 18, 2025, and indicated no current plans for an advisory committee meeting.
The BLA submission is supported by data from the pivotal Transpher A and long-term follow-up studies presented at WORLDSymposium™ 2025. Results showed rapid and sustained decreases in heparan sulfate levels in cerebrospinal fluid, with statistically significant improvements in Bayley-III scores for cognition and communication compared to untreated patients. Treatment-related adverse events were primarily mild to moderate liver enzyme elevations that resolved.
Ultragenyx Pharmaceutical (NASDAQ: RARE) ha annunciato l'accettazione da parte della FDA della loro Domanda di Licenza Biologica (BLA) per UX111, una terapia genica AAV mirata alla sindrome di Sanfilippo di tipo A (MPS IIIA). La FDA ha concesso una Revisione Prioritaria con una data PDUFA fissata per il 18 agosto 2025 e ha indicato che non ci sono piani attuali per una riunione del comitato consultivo.
La presentazione della BLA è supportata da dati degli studi pivotal Transpher A e di follow-up a lungo termine presentati al WORLDSymposium™ 2025. I risultati hanno mostrato rapidi e sostenuti decrementi nei livelli di solfato di eparina nel liquido cerebrospinale, con miglioramenti statisticamente significativi nei punteggi Bayley-III per la cognizione e la comunicazione rispetto ai pazienti non trattati. Gli eventi avversi correlati al trattamento erano principalmente lievi o moderati innalzamenti degli enzimi epatici che si sono risolti.
Ultragenyx Pharmaceutical (NASDAQ: RARE) anunció la aceptación por parte de la FDA de su Solicitud de Licencia Biológica (BLA) para UX111, una terapia génica AAV dirigida al síndrome de Sanfilippo tipo A (MPS IIIA). La FDA otorgó una Revisión Prioritaria con una fecha PDUFA del 18 de agosto de 2025 y no indicó planes actuales para una reunión del comité asesor.
La presentación de la BLA está respaldada por datos de los estudios pivotal Transpher A y de seguimiento a largo plazo presentados en el WORLDSymposium™ 2025. Los resultados mostraron disminuciones rápidas y sostenidas en los niveles de sulfato de heparina en el líquido cefalorraquídeo, con mejoras estadísticamente significativas en las puntuaciones de Bayley-III para la cognición y la comunicación en comparación con pacientes no tratados. Los eventos adversos relacionados con el tratamiento fueron principalmente elevaciones leves a moderadas de las enzimas hepáticas que se resolvieron.
울트라제닉스 제약 (NASDAQ: RARE)는 UX111에 대한 생물학적 라이센스 신청(BLA)이 FDA에 의해 수용되었음을 발표했습니다. 이는 AAV 유전자 치료제로, 샌필리포 증후군 A형(MPS IIIA)을 목표로 합니다. FDA는 우선 심사를 부여했으며, PDUFA 날짜는 2025년 8월 18일로 설정되었고 자문 위원회 회의에 대한 현재 계획은 없다고 밝혔습니다.
BLA 제출은 WORLDSymposium™ 2025에서 발표된 주요 Transpher A 연구 및 장기 추적 연구의 데이터를 기반으로 하고 있습니다. 결과는 치료받지 않은 환자와 비교하여 인지 및 의사소통을 위한 Bayley-III 점수의 통계적으로 유의미한 개선과 함께 뇌척수액 내 헤파란 황산염 수준의 빠르고 지속적인 감소를 보여주었습니다. 치료와 관련된 부작용은 주로 경미하거나 중등도의 간 효소 상승이었으며, 이는 해결되었습니다.
Ultragenyx Pharmaceutical (NASDAQ: RARE) a annoncé l'acceptation par la FDA de sa Demande de Licence Biologique (BLA) pour UX111, une thérapie génique AAV ciblant le syndrome de Sanfilippo de type A (MPS IIIA). La FDA a accordé une Révision Prioritaire avec une date PDUFA fixée au 18 août 2025 et a indiqué qu'il n'y a actuellement aucun projet de réunion du comité consultatif.
La soumission de la BLA est soutenue par des données des études pivotales Transpher A et de suivi à long terme présentées au WORLDSymposium™ 2025. Les résultats ont montré des diminutions rapides et soutenues des niveaux de sulfate d'héparine dans le liquide céphalorachidien, avec des améliorations statistiquement significatives des scores Bayley-III pour la cognition et la communication par rapport aux patients non traités. Les événements indésirables liés au traitement étaient principalement des élévations légères à modérées des enzymes hépatiques qui se sont résolues.
Ultragenyx Pharmaceutical (NASDAQ: RARE) gab die Annahme ihres Biologics License Application (BLA) für UX111 durch die FDA bekannt, eine AAV-Gentherapie, die auf das Sanfilippo-Syndrom Typ A (MPS IIIA) abzielt. Die FDA gewährte Prioritätsprüfung mit einem PDUFA-Datum vom 18. August 2025 und gab an, dass derzeit keine Pläne für eine Sitzung des Beratergremiums bestehen.
Die BLA-Einreichung wird durch Daten aus der entscheidenden Transpher A-Studie und Langzeitnachbeobachtungen unterstützt, die beim WORLDSymposium™ 2025 präsentiert wurden. Die Ergebnisse zeigten schnelle und nachhaltige Abnahmen der Heparansulfatwerte in der Rückenmarksflüssigkeit, mit statistisch signifikanten Verbesserungen der Bayley-III-Werte für Kognition und Kommunikation im Vergleich zu unbehandelten Patienten. Therapiebedingte unerwünschte Ereignisse waren hauptsächlich leichte bis moderate Erhöhungen der Leberenzyme, die sich zurückbildeten.
- FDA granted Priority Review status, accelerating the approval timeline
- No advisory committee meeting planned, potentially streamlining the approval process
- Clinical data showed statistically significant improvement in cognitive and communication scores
- Treatment demonstrated sustained reduction in heparan sulfate levels
- If approved, UX111 would be the first-ever treatment for Sanfilippo syndrome type A
- Treatment caused liver enzyme elevations as adverse events
Insights
The FDA's acceptance of Ultragenyx's BLA for UX111 with Priority Review status represents a pivotal development in the rare disease space. Priority Review designation, typically granted to therapies that could provide significant improvements in the treatment of serious conditions, reduces the standard review period from 10 to 6 months, potentially accelerating the path to market for this first-in-class therapy.
The clinical data package shows compelling evidence of efficacy through two critical measures: reduction in CSF heparan sulfate levels (a key biomarker) and improvements in cognitive and communication functions. This dual demonstration of biochemical and clinical efficacy is particularly noteworthy in the context of Sanfilippo syndrome type A, a devastating lysosomal storage disorder that typically results in severe neurodegeneration and early death, with no currently approved treatments.
Several factors enhance the probability of approval:
- The FDA's decision to forgo an advisory committee meeting suggests comfort with the data package and approval pathway
- The safety profile appears manageable, with primarily transient liver enzyme elevations
- The established correlation between biomarker improvement and clinical outcomes strengthens the accelerated approval case
The broader implications extend beyond UX111 itself. Success here could validate Ultragenyx's platform approach to neuronopathic MPS diseases, potentially creating a blueprint for other rare genetic disorders affecting the central nervous system. This could significantly expand the company's addressable market and technological leadership in the space.
From a commercial perspective, rare disease gene therapies typically command premium pricing, often in the
FDA decision expected by August 18, 2025
NOVATO, Calif., Feb. 18, 2025 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced the U.S. Food and Drug Administration (FDA or the Agency) has accepted for review the Biologics License Application (BLA) seeking accelerated approval for UX111 (ABO-102) AAV gene therapy as a treatment for patients with Sanfilippo syndrome type A (MPS IIIA). The FDA granted the BLA Priority Review with a Prescription Drug User Fee Act (PDUFA) action date of August 18, 2025. The FDA also informed the company that they are not currently planning to hold an advisory committee meeting to discuss this application.
“Acceptance of the UX111 BLA brings us closer to being able to provide a first-ever treatment for Sanfilippo syndrome type A and, if our application is successful, we’re prepared to launch this therapy for patients and their families,” said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. “By reaching alignment with the Agency on a path forward for accelerated approval in neuronopathic MPS diseases, our UX111 program could serve as a step towards advancing drug development across multiple metabolic diseases of the brain.”
The BLA submission for UX111 is supported by available data, including the latest data from the ongoing pivotal Transpher A and long-term follow-up studies presented at WORLDSymposium™ 2025, demonstrating treatment with UX111 resulted in rapid and sustained decreased levels of heparan sulfate (HS) in cerebrospinal fluid (CSF) in patients with Sanfilippo syndrome type A irrespective of age or stage of disease progression at the time of treatment. The data showed a statistically significant improvement in the Bayley-III raw scores for the subdomains of cognition, receptive communication and expressive communication in the modified intent-to-treat (mITT) group compared to natural history data from untreated patients. These clinical endpoints were correlated with substantial and sustained reduction in levels of CSF-HS. The most frequently reported treatment-related adverse events to date were elevations in liver enzymes, and the majority of these events were mild (Grade 1) or moderate (Grade 2) in severity and all resolved.
About UX111
UX111 is a novel in vivo gene therapy in Phase 1/2/3 development for Sanfilippo syndrome type A (MPS IIIA), a rare fatal lysosomal storage disease with no approved treatment that primarily affects the brain. The therapy is designed to address the underlying SGSH enzyme deficiency responsible for abnormal accumulation of heparan sulfate, a glycosaminoglycan, in the brain that results in progressive cell damage and neurodegeneration. UX111 is dosed in a one-time intravenous infusion using a self-complementary AAV9 vector to deliver a functional copy of the SGSH gene to cells. These transduced cells then produce the enzyme and secrete it to be taken up by other brain cells, cross-correcting the enzyme deficiency. The product was originally developed by Abeona Therapeutics and transferred to Ultragenyx to complete development. The UX111 program has received Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations in the U.S., and PRIME and Orphan medicinal product designations in the EU. If approved, the product will be commercialized with Ultragenyx’s existing metabolic disease team seeing the same biochemical genetics doctors.
About Sanfilippo Syndrome Type A (MPS IIIA)
Sanfilippo syndrome type A (MPS IIIA) is a rare, fatal lysosomal storage disease with no approved treatment that primarily affects the brain and is characterized by rapid neurodegeneration, with onset in early childhood. Children with MPS IIIA present with global developmental delay which eventually leads to progressive cognitive, language and motor decline, behavioral abnormalities and early death. MPS IIIA is estimated to affect approximately 3,000 to 5,000 patients in commercially accessible geographies with a median life expectancy of 15 years. MPS IIIA is caused by biallelic pathogenic variants in the SGSH gene that lead to a deficiency in the sulfamidase (SGSH) enzyme responsible for breaking down heparan sulfate, a glycosaminoglycans, which accumulate in cells throughout the body resulting in the observed rapid neurodegeneration that is associated with the disorder.
About Ultragenyx
Ultragenyx is a biopharmaceutical company committed to bringing novel therapies to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved medicines and treatment candidates aimed at addressing diseases with high unmet medical need and clear biology, for which there are typically no approved therapies treating the underlying disease.
The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.
For more information on Ultragenyx, please visit the company's website at: www.ultragenyx.com.
Forward-Looking Statements and Use of Digital Media
Except for the historical information contained herein, the matters set forth in this press release, including statements related to Ultragenyx's expectations and projections regarding its future operating results and financial performance, business plans and objectives for UX111, expectations regarding the tolerability and safety of UX111, and future clinical and regulatory developments for UX111 are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration with third parties, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainty of clinical drug development and unpredictability and lengthy process for obtaining regulatory approvals, the ability of the company to successfully develop UX111, the company’s ability to achieve its projected development goals in its expected timeframes, risks related to adverse side effects, risks related to reliance on third party partners to conduct certain activities on the company’s behalf, smaller than anticipated market opportunities for the company’s products and product candidates, manufacturing risks, competition from other therapies or products, and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the company’s future operating results and financial performance, the timing of clinical trial activities and reporting results from same, and the availability or commercial potential of Ultragenyx’s products and drug candidates. Ultragenyx undertakes no obligation to update or revise any forward-looking statements.
For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of Ultragenyx in general, see Ultragenyx's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 6, 2024, and its subsequent periodic reports filed with the SEC.
In addition to its SEC filings, press releases and public conference calls, Ultragenyx uses its investor relations website and social media outlets to publish important information about the company, including information that may be deemed material to investors, and to comply with its disclosure obligations under Regulation FD. Financial and other information about Ultragenyx is routinely posted and is accessible on Ultragenyx’s Investor Relations website (https://ir.ultragenyx.com/) and LinkedIn website (https://www.linkedin.com/company/ultragenyx-pharmaceutical-inc-/mycompany/).
Contacts
Ultragenyx Pharmaceutical Inc.
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ir@ultragenyx.com
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