Denali Therapeutics Announces Initiation of BLA Filing for Accelerated Approval of Tividenofusp Alfa for the Treatment of Hunter Syndrome (MPS II) and Positive Ongoing Interactions with FDA on DNL126 Through START Program
Denali Therapeutics (NASDAQ: DNLI) has initiated a rolling submission of a biologics license application (BLA) for accelerated approval of tividenofusp alfa to treat Hunter syndrome (MPS II). The submission has been received by the FDA's Center for Drug Evaluation and Research (CDER).
The company reports alignment with CDER on the BLA data package, including using cerebrospinal fluid heparan sulfate as a surrogate endpoint for accelerated approval. Denali expects to complete the BLA submission by first half of May 2025, with potential U.S. commercial launch anticipated in late 2025 or early 2026.
Additionally, Denali continues productive collaboration with CDER through the START program, focusing on an accelerated development and approval path for DNL126, targeting Sanfilippo syndrome treatment.
Denali Therapeutics (NASDAQ: DNLI) ha avviato una presentazione continua di una domanda di licenza biologica (BLA) per l'approvazione accelerata di tividenofusp alfa per il trattamento della sindrome di Hunter (MPS II). La domanda è stata ricevuta dal Centro per la Valutazione e la Ricerca dei Farmaci (CDER) della FDA.
L'azienda riferisce di essere in linea con il CDER riguardo al pacchetto di dati BLA, inclusa l'utilizzazione del solfato di eparina nel liquido cerebrospinale come endpoint surrogato per l'approvazione accelerata. Denali prevede di completare la presentazione della BLA entro la prima metà di maggio 2025, con un possibile lancio commerciale negli Stati Uniti previsto per la fine del 2025 o l'inizio del 2026.
Inoltre, Denali continua una collaborazione produttiva con il CDER attraverso il programma START, concentrandosi su un percorso di sviluppo e approvazione accelerato per il trattamento della sindrome di Sanfilippo (DNL126).
Denali Therapeutics (NASDAQ: DNLI) ha iniciado una presentación continua de una solicitud de licencia biológica (BLA) para la aprobación acelerada de tividenofusp alfa para tratar el síndrome de Hunter (MPS II). La solicitud ha sido recibida por el Centro de Evaluación e Investigación de Medicamentos (CDER) de la FDA.
La empresa informa que está alineada con el CDER sobre el paquete de datos de la BLA, incluyendo el uso de sulfato de heparina en el líquido cefalorraquídeo como un punto final sustituto para la aprobación acelerada. Denali espera completar la presentación de la BLA para la primera mitad de mayo de 2025, con un posible lanzamiento comercial en EE. UU. anticipado para finales de 2025 o principios de 2026.
Además, Denali continúa una colaboración productiva con el CDER a través del programa START, enfocándose en un camino de desarrollo y aprobación acelerado para el tratamiento de la síndrome de Sanfilippo (DNL126).
데날리 테라퓨틱스 (NASDAQ: DNLI)는 헌터 증후군 (MPS II) 치료를 위한 티비데노푸스 알파의 가속 승인에 대한 생물학적 라이센스 신청서 (BLA)의 롤링 제출을 시작했습니다. 이 제출은 FDA의 의약품 평가 및 연구 센터 (CDER)에 접수되었습니다.
회사는 BLA 데이터 패키지에 대해 CDER와의 일치를 보고하며, 가속 승인을 위한 대체 최종점으로 뇌척수액 내 헤파란 황산염을 사용하는 것을 포함합니다. 데날리는 2025년 5월 상반기까지 BLA 제출을 완료할 것으로 예상하며, 2025년 말 또는 2026년 초에 미국 상업 출시가 예상됩니다.
또한, 데날리는 START 프로그램을 통해 CDER와의 생산적인 협력을 계속하고 있으며, 샌필리포 증후군 치료를 위한 DNL126의 가속 개발 및 승인 경로에 집중하고 있습니다.
Denali Therapeutics (NASDAQ: DNLI) a lancé une soumission continue d'une demande de licence biologique (BLA) pour une approbation accélérée de tividenofusp alfa pour traiter le syndrome de Hunter (MPS II). La soumission a été reçue par le Centre d'évaluation et de recherche des médicaments (CDER) de la FDA.
L'entreprise rapporte être en accord avec le CDER concernant le paquet de données BLA, y compris l'utilisation du sulfate d'héparine dans le liquide céphalorachidien comme critère de substitution pour l'approbation accélérée. Denali prévoit de finaliser la soumission de la BLA d'ici la première moitié de mai 2025, avec un lancement commercial aux États-Unis prévu pour fin 2025 ou début 2026.
De plus, Denali continue une collaboration productive avec le CDER à travers le programme START, se concentrant sur un parcours de développement et d'approbation accéléré pour le traitement du syndrome de Sanfilippo (DNL126).
Denali Therapeutics (NASDAQ: DNLI) hat eine fortlaufende Einreichung eines Antrags auf biologische Lizenz (BLA) für die beschleunigte Zulassung von Tividenofusp Alfa zur Behandlung des Hunter-Syndroms (MPS II) initiiert. Der Antrag wurde vom Zentrum für Arzneimittelbewertung und -forschung (CDER) der FDA erhalten.
Das Unternehmen berichtet von einer Übereinstimmung mit dem CDER bezüglich des BLA-Datenpakets, einschließlich der Verwendung von Heparansulfat im Liquor cerebrospinalis als surrogate Endpunkt für die beschleunigte Zulassung. Denali erwartet, die BLA-Einreichung bis zur ersten Hälfte Mai 2025 abzuschließen, mit einer möglichen geplanten kommerziellen Markteinführung in den USA Ende 2025 oder Anfang 2026.
Darüber hinaus setzt Denali die produktive Zusammenarbeit mit dem CDER im Rahmen des START-Programms fort, das sich auf einen beschleunigten Entwicklungs- und Zulassungsweg für DNL126 konzentriert, das die Behandlung des Sanfilippo-Syndroms zum Ziel hat.
- FDA acceptance of rolling BLA submission for tividenofusp alfa
- Alignment with FDA on accelerated approval pathway using surrogate endpoint
- Clear commercialization timeline with potential launch in late 2025/early 2026
- Progress on DNL126 through FDA's START program for additional indication
- Commercial launch not expected until late 2025 at earliest
- Still pending full BLA submission and approval
- Accelerated approval pathway requires post-approval confirmation of clinical benefit
Insights
Denali's initiation of a rolling BLA submission for tividenofusp alfa represents a significant regulatory milestone that substantially de-risks their pathway to potential commercialization. The FDA's acceptance of this rolling submission is particularly noteworthy for several reasons:
First, the alignment with CDER on using cerebrospinal fluid heparan sulfate as a surrogate endpoint for accelerated approval is crucial. This biomarker-based approach can significantly compress the development timeline for rare diseases like Hunter syndrome where traditional clinical endpoints might require years of observation or larger patient populations.
Second, the company has secured clarity on both the accelerated approval pathway and the subsequent conversion to full approval. This regulatory certainty removes significant uncertainty from the development process and provides a well-defined roadmap to potential commercialization.
The projected BLA completion by May 2025 with potential launch in late 2025/early 2026 indicates confidence in the submission package and suggests productive pre-submission interactions with regulators. The FDA's START program involvement with DNL126 for Sanfilippo syndrome further validates Denali's regulatory strategy and approach to rare disease treatments.
This dual-program progress demonstrates the potential scalability of Denali's Enzyme Transport Vehicle platform across multiple lysosomal storage disorders, suggesting a broader application of their technology beyond a single indication. The rolling review process itself is typically reserved for treatments addressing serious conditions with high unmet need, reflecting the FDA's assessment of the therapy's potential importance.
This regulatory advancement represents a critical value inflection point for Denali as they progress toward potential commercialization in the rare disease space. Hunter syndrome (MPS II) represents a serious genetic disorder with treatment options that primarily address peripheral symptoms but not the neurological manifestations of the disease.
The acceptance of a rolling BLA submission signals transition toward commercial-stage operations, with Denali actively preparing for a potential U.S. launch. For a company with a
Tividenofusp alfa's differentiation lies in its ability to cross the blood-brain barrier using Denali's proprietary Enzyme Transport Vehicle technology, potentially addressing the neurological symptoms that current therapies cannot effectively treat. This same platform technology is being leveraged for DNL126 in Sanfilippo syndrome, validating the broader application of their scientific approach.
The defined regulatory pathway, including acceptance of surrogate endpoints, substantially reduces execution risk. Rare disease therapies typically command premium pricing, and with Hunter syndrome affecting approximately 1 in 100,000-170,000 males, even a small patient population could translate to meaningful revenue.
The dual-program advancement also demonstrates pipeline depth beyond a single asset, an important consideration for biotech valuation. While regulatory hurdles remain before final approval, this milestone represents significant progress in Denali's evolution toward becoming a commercial-stage rare disease company with a platform technology that could yield multiple products.
- Rolling submission of BLA initiated for tividenofusp alfa; preparations ongoing for potential U.S. commercial launch in late 2025 or early 2026
- Alignment through recent interactions with CDER on path to accelerated approval and conversion to full approval for tividenofusp alfa
- Productive collaboration continues under START for an accelerated development and approval path for DNL126
SOUTH SAN FRANCISCO, Calif., April 02, 2025 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (NASDAQ: DNLI), today announced that the company’s initiation of a rolling submission of a biologics license application (BLA) for accelerated approval of tividenofusp alfa for the treatment of Hunter syndrome (MPS II) has been received by the Center for Drug Evaluation and Research (CDER) of the U.S. Food and Drug Administration (FDA). Denali continues to have regular, collaborative, and productive engagement with CDER and is aligned with CDER on the content of the BLA data package, including the use of cerebrospinal fluid heparan sulfate (CSF HS) as a surrogate endpoint to support an accelerated approval, as well as the full approval conversion path. Denali expects to complete the BLA submission in the first half of May 2025 and continues to prepare for a potential commercial launch in the U.S. in late 2025 or early 2026.
“We are grateful to the FDA for their ongoing support of our BLA filing and continued dedication to advance new medicines,” said Carole Ho, M.D., Chief Medical Officer of Denali. “This regulatory milestone brings us closer to our goal of delivering a new treatment option to the Hunter syndrome community as we continue to listen, learn, and seek their advice in bringing tividenofusp alfa to patients. Our progress has broader positive implications supporting the expansion of our Enzyme TransportVehicle franchise of next-generation enzyme replacement therapies to treat the brain and body. In this context, we appreciate the ongoing and productive collaboration with CDER through the START program as we align on an accelerated development and approval path for DNL126 for the potential treatment of Sanfilippo syndrome.”
About Hunter Syndrome (MPS II)
Hunter syndrome (MPS II) is a rare genetic disease that affects over 2,000 individuals worldwide, primarily males, and leads to physical, cognitive, and behavioral symptoms. Hunter syndrome is caused by mutations in the iduronate-2-sulfatase (IDS) gene, which leads to a deficiency of the IDS enzyme. Symptoms often begin emerging around age two and include physical complications, including organ dysfunction, joint stiffness, hearing loss and impaired growth, and neurocognitive symptoms with impaired development. The disease is characterized by a buildup of glycosaminoglycans (GAGs) in lysosomes — the part of the cell that breaks down materials including GAGs. The current standard of care, enzyme replacement therapy, partially treats physical symptoms but does not cross the blood-brain barrier, and as a result, cognitive and behavioral symptoms experienced by the majority of patients with Hunter syndrome are not addressed. Therapies that address the range of cognitive, behavioral, and physical manifestations of the disease are recognized as an unmet need for this patient community.1
About Tividenofusp Alfa
Tividenofusp alfa (or DNL310) is composed of the iduronate 2-sulfatase (IDS) enzyme fused to Denali’s proprietary Enzyme TransportVehicle™ (ETV), uniquely designed to deliver IDS into the brain and the body, with the goal of addressing behavioral, cognitive, and physical symptoms of Hunter syndrome (MPS II). The U.S. Food and Drug Administration has granted Fast Track and Breakthrough Therapy designations to tividenofusp alfa for development in the treatment of Hunter syndrome (MPS II). The European Medicines Agency has granted Priority Medicines designation to tividenofusp alfa.
The Phase 2/3 COMPASS study is enrolling participants with MPS II in North America, South America, and Europe to support global approval. Participants are randomized 2:1 to receive either tividenofusp alfa or idursulfase, respectively. More information about the COMPASS study can be found here.
Tividenofusp alfa is an investigational therapeutic and has not been approved for use by any Health Authority.
About Sanfilippo Syndrome Type A (MPS IIIA)
MPS III, also called Sanfilippo syndrome, is a rare, genetic lysosomal storage disease that causes neurodegeneration. There are four main types of MPS III, depending on the enzyme affected. Type A is caused by genetic defects that result in reduction in the activity of N-sulfoglucosamine sulfohydrolase (SGSH), an enzyme responsible for degrading heparan sulfate in the lysosome. There are no approved treatments for MPS IIIA.
About DNL126 (ETV:SGSH)
DNL126 (ETV:SGSH) is an intravenously administered, Enzyme TransportVehicle™ (ETV)-enabled SGSH replacement therapy designed to cross the BBB via receptor-mediated transcytosis into the brain and to enable broad delivery of SGSH into cells and tissues throughout the body with the goal of addressing the behavioral, cognitive, and physical manifestations of MPS IIIA.
DNL126 is an investigational therapeutic and has not been approved for use by any Health Authority.
About the Phase 1/2 study of DNL126
Denali is conducting a multicenter, open-label, Phase 1/2 study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory clinical efficacy of DNL126 in participants with MPS IIIA. The core study period is approximately 6 months and is followed by an open-label extension for approximately 18 months. More information about the Phase 1/2 study can be found here.
About Denali Therapeutics
Denali Therapeutics is a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier for neurodegenerative diseases and lysosomal storage diseases. Denali pursues new treatments by rigorously assessing genetically validated targets, engineering delivery across the blood-brain barrier and guiding development through biomarkers that demonstrate target and pathway engagement. Denali is based in South San Francisco. For additional information, please visit www.denalitherapeutics.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding plans, timelines, and expectations related to Denali's Enzyme TransportVehicle™ (TV) platform and its therapeutic and commercial potential; plans, timelines, and expectations relating to tividenofusp alfa (DNL310), including enrollment in the ongoing global Phase 2/3 COMPASS study, the timing of completion of its BLA submission, the likelihood of accelerated and full approval, and the timing and likelihood of commercial launch; expectations for ongoing communications with the FDA; plans, timelines, and expectations related to DNL126, including enrollment in and timing of the Phase 1/2 study; and statements made by Denali’s Chief Medical Officer. Actual results may differ materially from those expressed or implied by these forward-looking statements due to a variety of risks and uncertainties. These include, but are not limited to: risks arising from adverse economic conditions and their impact on Denali’s business and operations; the possibility of events or changes that could lead to the termination of Denali’s collaboration agreements; challenges associated with Denali’s transition to a late-stage clinical drug development company; the ability of Denali and its collaborators to complete the development and, if approved, the commercialization of product candidates; difficulties in patient enrollment for ongoing and future clinical trials; reliance on third-party manufacturers and suppliers for clinical trial materials; dependence on the successful development of Denali’s blood-brain barrier platform technology and related programs; potential delays or failures in meeting expected clinical trial timelines; the risk that promising preclinical profiles may not be replicated in clinical settings; discrepancies between preclinical, early-stage, or preliminary clinical results and outcomes from later-stage trials; the occurrence of significant adverse events or other undesirable side effects; and the uncertainty surrounding regulatory approvals required for commercialization; Denali’s ability to advance a pipeline of product candidates or develop commercially successful products; developments relating to Denali's competitors and its industry, including competing product candidates and therapies; Denali’s ability to obtain, maintain, or protect intellectual property rights related to its product candidates; implementation of Denali’s strategic plans for its business, product candidates, and blood-brain barrier platform technology; Denali's ability to obtain additional capital to finance its operations, as needed; Denali's ability to accurately forecast future financial results in the current environment; and other risks and uncertainties, including those described in Denali's most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 27, 2025 and Denali’s future reports to be filed with the SEC. Denali's product candidates are investigational, and their safety and efficacy profiles have not yet been established. No Denali product candidates have been approved by any health authority for any use. Denali does not undertake any obligation to update or revise any forward-looking statements, to conform these statements to actual results or to make changes in Denali’s expectations, except as required by law.
Reference
- Muenzer, J., et al. Community consensus for Heparan sulfate as a biomarker to support accelerated approval in Neuronopathic Mucopolysaccharidoses. Mol Genet Metab. 2024 Aug;142(4):108535
| Investor Contact Laura Hansen, Ph.D. Vice President, Investor Relations (650) 452-2747 hansen@dnli.com | Media Contact Rich Allan FGS Global (503) 851-0807 rich.allan@fgsglobal.com |
FAQ
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