Ultragenyx Submits Biologics License Application to the U.S. FDA for UX111 AAV Gene Therapy for the Treatment of Sanfilippo Syndrome Type A (MPS IIIA)
Ultragenyx Pharmaceutical (NASDAQ: RARE) has submitted a Biologics License Application (BLA) to the FDA for UX111, an AAV gene therapy targeting Sanfilippo Syndrome Type A (MPS IIIA). If approved, UX111 would become the first authorized treatment in the U.S. for this condition.
The submission follows FDA's acceptance of cerebral spinal fluid (CSF) heparan sulfate (HS) as a surrogate endpoint for accelerated approval. Data from the ongoing pivotal Transpher A study showed that UX111 treatment led to rapid and sustained decreases in CSF HS levels, correlating with improved long-term cognitive development compared to natural history data. Most treatment-related adverse events were mild to moderate liver enzyme elevations that resolved.
Ultragenyx Pharmaceutical (NASDAQ: RARE) ha presentato una Domanda di Licenza Biologica (BLA) alla FDA per UX111, una terapia genica AAV per il trattamento della Sindrome di Sanfilippo Tipo A (MPS IIIA). Se approvato, UX111 diventerà il primo trattamento autorizzato negli Stati Uniti per questa condizione.
La presentazione è avvenuta dopo che la FDA ha accettato il solfato di eparina (HS) nel liquido cerebrospinale (CSF) come indicatore surrogato per l'approvazione accelerata. I dati dello studio pivotale in corso Transpher A hanno mostrato che il trattamento con UX111 ha portato a riduzioni rapide e sostenute dei livelli di HS nel CSF, correlando con un miglioramento nello sviluppo cognitivo a lungo termine rispetto ai dati di storia naturale. La maggior parte degli eventi avversi correlati al trattamento sono stati lievi o moderati rialzi degli enzimi epatici che si sono risolti.
Ultragenyx Pharmaceutical (NASDAQ: RARE) ha presentado una Solicitud de Licencia Biológica (BLA) a la FDA para UX111, una terapia génica AAV dirigida a la Síndrome de Sanfilippo Tipo A (MPS IIIA). Si se aprueba, UX111 se convertirá en el primer tratamiento autorizado en EE. UU. para esta condición.
La presentación sigue a la aceptación por parte de la FDA del sulfato de heparina (HS) en el líquido cefalorraquídeo (CSF) como un punto final sustituto para la aprobación acelerada. Los datos del estudio pivotal Transpher A en curso mostraron que el tratamiento con UX111 llevó a disminuciones rápidas y sostenidas de los niveles de HS en el CSF, lo que correlaciona con un mejor desarrollo cognitivo a largo plazo en comparación con los datos de historia natural. La mayoría de los eventos adversos relacionados con el tratamiento fueron aumentos leves a moderados de las enzimas hepáticas que se resolvieron.
Ultragenyx Pharmaceutical (NASDAQ: RARE)가 UX111에 대한 생물학적 제품 허가 신청(BLA)을 FDA에 제출했습니다. 이는 AAV 유전자 요법으로, 산필리포 증후군 타입 A(MPS IIIA)를 치료하는 것입니다. 승인된다면, UX111은 미국에서 이 질환에 대한 첫 번째 승인 치료제가 될 것입니다.
이번 제출은 FDA가 가속 승인을 위한 대리 지표로서 뇌척수액(CSF) 내의 헤파란 황산(HS)을 수용한 이후 이루어졌습니다. 진행 중인 주요 연구인 Transpher A에서의 데이터는 UX111 치료가 CSF HS 수준을 신속하고 지속적으로 감소시켰으며, 이것이 자연 발생 데이터에 비해 장기적인 인지 발달 개선과 일치함을 보여주었습니다. 치료와 관련된 대부분의 부작용은 경미한 정도에서 중간 정도의 간 효소 상승이었으며, 이는 해소되었습니다.
Ultragenyx Pharmaceutical (NASDAQ: RARE) a soumis une Demande de Licence Biologique (BLA) à la FDA pour UX111, une thérapie génique AAV ciblant le syndrome de Sanfilippo de type A (MPS IIIA). Si elle est approuvée, UX111 deviendra le premier traitement autorisé aux États-Unis pour cette condition.
La soumission fait suite à l'acceptation par la FDA du sulfate d'héparine (HS) dans le liquide céphalorachidien (CSF) comme critère intermédiaire pour une approbation accélérée. Les données de l'étude pivotale en cours Transpher A ont montré que le traitement par UX111 entraînait des réductions rapides et durables des niveaux de HS dans le CSF, corrélant avec une amélioration du développement cognitif à long terme par rapport aux données historiques. La plupart des événements indésirables liés au traitement étaient des élévations des enzymes hépatiques de faible à modérée intensité qui se sont résolues.
Ultragenyx Pharmaceutical (NASDAQ: RARE) hat einen Antrag auf Biologisches Lizenzverfahren (BLA) bei der FDA für UX111 eingereicht, eine AAV-Gentherapie zur Behandlung des Sanfilippo-Syndroms Typ A (MPS IIIA). Bei Genehmigung würde UX111 die erste autorisierte Behandlung in den USA für diese Erkrankung werden.
Die Einreichung folgt auf die Akzeptanz der FDA, dass Heparansulfat (HS) im zerebrospinalen Flüssigkeit (CSF) als Surrogatendpunkt für eine beschleunigte Genehmigung verwendet werden kann. Daten aus der laufenden entscheidenden Transpher A-Studie zeigten, dass die Behandlung mit UX111 zu schnellen und nachhaltigen Abnahmen der HS-Spiegel im CSF führte, was mit einer Verbesserung der langfristigen kognitiven Entwicklung im Vergleich zu den Daten der natürlichen Geschichte korrelierte. Die meisten behandlungsbedingten unerwünschten Ereignisse waren milde bis moderate Erhöhungen der Leberenzyme, die sich zurückbildeten.
- First potential FDA-approved therapy for Sanfilippo Syndrome Type A
- FDA acceptance of CSF heparan sulfate as surrogate endpoint enables accelerated approval pathway
- Clinical data shows improved cognitive development compared to natural history
- Treatment demonstrated rapid and sustained decrease in disease biomarkers
- Treatment-related adverse events include liver enzyme elevations
Insights
This BLA submission for UX111 represents a pivotal milestone in rare disease therapeutics. The use of CSF heparan sulfate as a surrogate endpoint for accelerated approval is groundbreaking - it's the first time this biomarker has been accepted by the FDA for MPS disorders. The clinical data showing sustained reduction in CSF HS correlating with improved cognitive development versus natural history is particularly compelling.
The market opportunity is significant despite the ultra-rare nature of Sanfilippo Syndrome Type A. With no currently approved treatments in the U.S., UX111 would have first-mover advantage in this indication. Gene therapy treatments for rare diseases typically command premium pricing, often
The safety profile appears manageable, with primarily mild-to-moderate liver enzyme elevations that resolved. This favorable risk-benefit profile increases the likelihood of regulatory approval.
The FDA's acceptance of CSF heparan sulfate as a surrogate endpoint marks a watershed moment for rare disease drug development. This regulatory precedent could accelerate the development pathway for numerous other MPS disorders, potentially reducing the time and cost of bringing these therapies to market.
The submission under accelerated approval pathway is strategically sound. The FDA's prior agreement on the biomarker use, coupled with the compelling efficacy data and manageable safety profile, positions UX111 favorably for approval. Based on standard review timelines, we could expect a decision within 10-12 months, assuming Priority Review designation.
For investors unfamiliar with accelerated approval: Think of it as a "conditional green light" based on surrogate endpoints that reasonably predict clinical benefit, allowing faster access to potentially life-saving treatments while requiring post-approval confirmation of benefit.
If approved, UX111 would be the first approved therapy in the U.S. for Sanfilippo Syndrome Type A
NOVATO, Calif., Dec. 19, 2024 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA or the Agency) seeking accelerated approval for UX111 (ABO-102) AAV gene therapy as a treatment for patients with Sanfilippo syndrome type A (MPS IIIA).
“The path to get a treatment to the point of a BLA filing has been long and perilous for the Sanfilippo community. They have had to watch their children, once thriving, lose their ability to speak and walk, and eventually die, while research programs were shelved due to regulatory and funding hurdles,” said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. “We commend the FDA’s detailed evaluation and acceptance of cerebral spinal fluid (CSF) heparan sulfate (HS) as a well-characterized biomarker to support an accelerated approval pathway for mucopolysaccharidoses (MPS) disorders, including Sanfilippo syndrome. The FDA’s acceptance of CSF HS, which we define as a disease-cause biomarker since it measures the underlying disease, enabled us to file our BLA and may unlock the future accelerated approvals of a host of new therapies for these devastating MPS diseases that affect the brain.”
Earlier this year, Ultragenyx reached agreement with the Agency that CSF HS can be used as a surrogate endpoint for accelerated approval based on the body of data presented by the company, along with a consortium of academics and other industry sponsors at a workshop hosted by the Reagan-Udall Foundation for the FDA in February 2024.
The BLA submission for UX111 is supported by available data, including from the ongoing pivotal Transpher A study, demonstrating treatment with UX111 resulted in rapid and sustained decreased levels of HS in CSF in patients with Sanfilippo syndrome type A, and that sustained reduction in CSF HS exposure over time was correlated with improved long-term cognitive development compared to the decline observed during the same period of time in natural history data. 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. UX111 is designed to be dosed in a one-time intravenous infusion using a self-complementary AAV9 vector to deliver a functional copy of the SGSH gene to cells. 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. 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.
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 language and cognitive 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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FAQ
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