Denali Therapeutics Announces FDA Review Extension of BLA for Tividenofusp Alfa for the Treatment of MPS II (Hunter Syndrome)
Denali Therapeutics (Nasdaq: DNLI) said the FDA extended the PDUFA target date for its Biologics License Application for tividenofusp alfa to treat mucopolysaccharidosis type II (MPS II/Hunter syndrome) from Jan 5, 2026 to Apr 5, 2026.
The extension follows Denali’s submission of updated clinical pharmacology information and the FDA’s classification of that submission as a Major Amendment, which per FDA rules adds three months to review. Denali stated the amendment was not related to efficacy, safety, or biomarkers and that no additional data were requested. The company said it continues preparing for potential approval and commercial launch.
Denali Therapeutics (Nasdaq: DNLI) ha detto che la FDA ha esteso la data obiettivo PDUFA per la sua Biologics License Application per tividenofusp alfa per trattare la mucopolysaccharidosi di tipo II (sindrome di Hunter / MPS II) da 5 gennaio 2026 a 5 aprile 2026.
L’estensione segue la presentazione da parte di Denali di informazioni farmacologiche cliniche aggiornate e la classificazione da parte della FDA di tale presentazione come una Modifica Maggiore, che secondo le norme FDA aggiunge tre mesi alla valutazione. Denali ha dichiarato che la modifica non era correlata a efficacia, sicurezza o biomarcatori e che non sono stati richiesti ulteriori dati. L’azienda ha detto che continua a prepararsi per una potenziale approvazione e lancio commerciale.
Denali Therapeutics (Nasdaq: DNLI) dijo que la FDA extendió la fecha objetivo PDUFA para su Biologic License Application de tividenofusp alfa para tratar la mucopolisacaridosis tipo II (síndrome de Hunter / MPS II) desde 5 de enero de 2026 hasta 5 de abril de 2026.
La extensión sigue a la presentación por parte de Denali de información clínica farmacológica actualizada y la clasificación por parte de la FDA de esa presentación como una Enmienda Mayor, lo que según las normas de la FDA añade tres meses a la revisión. Denali afirmó que la enmienda no estaba relacionada con eficacia, seguridad o biomarcadores y que no se solicitaron datos adicionales. La empresa dijo que continúa preparándose para una posible aprobación y lanzamiento comercial.
Denali Therapeutics (나스닥: DNLI)는 FDA가 tividenofusp alfa의 생물학적 제제 면허 신청(BLA)에 대한 PDUFA 목표일을 2026년 1월 5일에서 2026년 4월 5일로 연장했다고 말했다. 이는 mucopolysaccharidosis II형(Hunter 증후군) 치료를 위한 것이다.
연장 조치는 Denali가 업데이트된 임상 약리학 정보를 제출했고 그 제출물이 FDA 규정에 따라 주요 수정(Major Amendment)로 분류되었기 때문이다. 이는 FDA 규정에 따라 심사에 3개월이 추가되는 것이다. Denali는 수정안이 효능, 안전성 또는 바이오마커와 관련이 없었으며 추가 데이터가 요청되지 않았다고 밝혔다. 회사는 잠재적 승인 및 상용 출시를 위한 준비를 계속하고 있다고 말했다.
Denali Therapeutics (NASDAQ : DNLI) a déclaré que la FDA a prolongé la date cible PDUFA pour sa Biologic License Application pour tividenofusp alfa afin de traiter la mucopolysaccharidose type II (syndrome de Hunter / MPS II) de 5 janvier 2026 à 5 avril 2026.
Cette extension fait suite à la soumission par Denali d'informations pharmacologiques cliniques mises à jour et à la classification de cette soumission par la FDA comme une Modification majeure, ce qui, selon les règles de la FDA, ajoute trois mois à l'examen. Denali a indiqué que la modification n'était pas liée à l'efficacité, à la sécurité ou aux biomarqueurs et qu'aucune donnée supplémentaire n'avait été demandée. L'entreprise a déclaré qu'elle poursuivait sa préparation à une éventuelle approbation et à un lancement commercial.
Denali Therapeutics (Nasdaq: DNLI) sagte, die FDA habe das PDUFA-Zieltermin für seine Biologics License Application für tividenofusp alfa zur Behandlung der Mucopolysaccharidose Typ II (Hunter-Syndrom) von 5. Januar 2026 auf 5. April 2026 verlängert.
Die Verlängerung folgt auf Denalis Einreichung aktualisierter klinischer Pharmakologie-Informationen und die FDA-Klassifizierung dieser Einreichung als Große Änderung, die nach FDA-Regeln die Prüfung um drei Monate verlängert. Denali erklärte, dass die Änderung nicht mit Wirksamkeit, Sicherheit oder Biomarkern zusammenhänge und dass keine zusätzlichen Daten angefordert wurden. Das Unternehmen sagte, es bereite sich weiter auf eine mögliche Genehmigung und Markteinführung vor.
Denali Therapeutics (بورصة ناسداك: DNLI) قالت إن إدارة الغذاء والدواء الأمريكية مددت تاريخ هدف PDUFA لطلبها للحصول على ترخيص دواء بيولوجي (tividenofusp alfa) لعلاج التخلف المينكوشاني من النوع II (متلازمة هانتر/MPS II) من 5 يناير 2026 إلى 5 أبريل 2026.
التمديد يأتي عقب تقديم Denali معلومات صيدلانية سريرية محدثة وتصنيفها من قبل FDA على أنها تعديل رئيسي، وهو ما يضيف وفق قواعد FDA ثلاثة أشهر إلى المراجعة. وأوضحت Denali أن التعديل لم يكن مرتبطاً بالفعالية أو السلامة أو المؤشرات الحيوية وأنه لم تُطلب بيانات إضافية. قالت الشركة إنها مستمرة في التحضير للموافقة المحتملة والإطلاق التجاري.
Denali Therapeutics (纳斯达克：DNLI) 表示 FDA 将其用于治疗黏蛋白聚糖贮积病II型（Hunter综合征/MPS II）的生物制剂许可申请（BLA）的 PDUFA 目标日期从 2026年1月5日 延长至 2026年4月5日。
延长期是 Denali 提交了更新的临床药理信息，FDA 将该提交分类为一个 重大修正，按 FDA 规则会在审评中增加三个月。Denali 表示该修正与有效性、安全性或生物标志物无关，且未要求额外数据。公司表示将继续为潜在的批准和商业上市做准备。
- PDUFA date extended to Apr 5, 2026
- FDA classified submission as a Major Amendment
- FDA requested no additional data in the MA letter
- Regulatory review delayed by three months
- Approval and commercial launch timing now uncertain until Apr 5, 2026
SOUTH SAN FRANCISCO, Calif., Oct. 13, 2025 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (Nasdaq: DNLI) today announced that the U.S. Food and Drug Administration (FDA) has extended its review timeline of the Biologics License Application (BLA) seeking accelerated approval of tividenofusp alfa for the treatment of mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome. The Prescription Drug User Fee Act (PDUFA) target date has been extended from January 5, 2026, to April 5, 2026.
The extension follows Denali’s submission of updated clinical pharmacology information in response to an information request from the FDA as part of the standard review process and is not related to efficacy, safety or biomarkers. The FDA classified the submission as a Major Amendment (MA) to the BLA, which, per FDA regulations, extends the review by three months. No additional data were requested by the FDA in the MA letter. Denali believes that the updated information submitted in the amendment does not affect the clinical pharmacology or benefit-risk conclusions of the BLA.
“We appreciate the FDA’s continued collaboration throughout the review process,” said Ryan Watts, Ph.D., Chief Executive Officer of Denali Therapeutics. “We continue to prepare for the potential approval and commercial launch of tividenofusp alfa. We feel the urgency to deliver for the MPS community, and we are committed to working together with regulators, physicians, and advocates to bring this important therapy to individuals and families living with Hunter syndrome.”
About Tividenofusp Alfa
Tividenofusp alfa (DNL310) is composed of the iduronate 2-sulfatase (IDS) enzyme fused to Denali’s proprietary TransportVehicle™ (TV) platform, 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 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 Hunter Syndrome (MPS II)
Hunter syndrome, also known as MPS II, is a rare genetic lysosomal storage disease caused by mutations in the iduronate-2-sulfatase (IDS) gene. This results in a deficiency of the IDS enzyme, which is responsible for breaking down glycosaminoglycans (GAGs) such as heparan sulfate and dermatan sulfate. The accumulation of GAGs leads to progressive damage in multiple organs and tissues, including the brain. Symptoms of Hunter syndrome include developmental delays, cognitive decline, behavioral abnormalities and physical complications such as joint stiffness, hearing loss and organ dysfunction. Current standard-of-care enzyme replacement therapies do not cross the blood-brain barrier and therefore do not address the neurological symptoms of the disease. There is a significant unmet need for therapies that address both the central nervous system (CNS) and peripheral manifestations of Hunter syndrome.
About Denali Therapeutics
Denali Therapeutics is a biotechnology company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for the treatment of neurodegenerative diseases and lysosomal storage diseases. Denali pursues new treatments by rigorously assessing genetically validated targets, engineering delivery across the BBB, 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.
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, plans, timelines and expectations relating to tividenofusp alfa, including the timing of the PDUFA action date, the likelihood of regulatory approval, expectations regarding the adequacy of clinical data to support the BLA, and the timing and likelihood of commercial launch; expectations for ongoing communications with the FDA; and statements made by Denali’s Chief Executive 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 that the PDUFA action date may be extended and the FDA may ultimately determine not to approve the BLA in its present form or at all; 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 and Quarterly Reports on Forms 10-K and 10-Q filed with the Securities and Exchange Commission (SEC) on February 27, 2025 and August 11, 2025, respectively, 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.
Investor Contact:
Laura Hansen, Ph.D.
Investor Relations
lhansen@dnli.com
Media Contact:
Erin Patton
Corporate Communications
epatton@dnli.com
FAQ
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