A Phase 2/3, Multicenter, Double-Blind, Randomized Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric and Young Adult Participants With Neuronopathic or Non-Neuronopathic Mucopolysaccharidosis Type II

This is a Phase 2/3, multiregional, two-arm, double-blind, randomized, active (standard-of-care)-controlled study of the efficacy and safety of tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant enzyme-replacement therapy (ERT) for mucopolysaccharidosis type II (MPS II).
Participants may also qualify to enter an open-label treatment phase with DNL310 or idursulfase based on pre-specified criteria.

开始日期2022-07-21

申办/合作机构

Denali Therapeutics, Inc.

NCT04251026

/ Active, not recruiting临床1/2期

A Phase 1/2, Multicenter, Open-Label Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL310 in Pediatric Participants With Hunter Syndrome

This is a multicenter, multiregional, open-label study to assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant enzyme replacement therapy (ERT), designed to treat both the peripheral and CNS manifestations of Mucopolysaccharidosis type II (MPS II; Hunter syndrome).
Participants, whose physicians feel they are deriving benefit, will have the opportunity to be reconsented into a safety extension and then an open-label extension for continued evaluation.

开始日期2020-07-16

申办/合作机构

Denali Therapeutics, Inc.

100 项与 Tividenofusp alfa 相关的临床结果

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100 项与 Tividenofusp alfa 相关的转化医学

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100 项与 Tividenofusp alfa 相关的专利（医药）

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项与 Tividenofusp alfa 相关的文献（医药）

2021-10-08·JCI insight1区 · 医学

Iduronate-2-sulfatase transport vehicle rescues behavioral and skeletal phenotypes in a mouse model of Hunter syndrome

1区 · 医学

ArticleOA

作者: Chiu, Chi-Lu ; Zhu, Yuda ; Tsogtbaatar, Buyankhishig ; Simms, Jeffrey ; Gill, Thomas M ; Speckart, Jessica ; Harris, Jeffrey M ; Costanzo, Simona ; Lopez, Isabel A ; Nguyen, Hoang N ; Thomsen, Elliot R ; Chan, Darren ; Henry, Anastasia G ; Holtzman, Julia ; Meisner, René ; Solanoy, Hilda ; Dugas, Jason C ; Henne, Kirk R ; Fang, Meng ; Delucchi, Anthony ; Arguello, Annie ; Sanchez, Pascal E ; Bhalla, Akhil ; Lo, Iris ; Diaz, Dolores ; Ravi, Ritesh ; Scearce-Levie, Kimberly ; Cheng, Yuhsiang

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder caused by deficiency of the iduronate-2-sulfatase (IDS) enzyme, resulting in cellular accumulation of glycosaminoglycans (GAGs) throughout the body. Treatment of MPS II remains a considerable challenge as current enzyme replacement therapies do not adequately control many aspects of the disease, including skeletal and neurological manifestations. We developed an IDS transport vehicle (ETV:IDS) that is engineered to bind to the transferrin receptor; this design facilitates receptor-mediated transcytosis of IDS across the blood-brain barrier and improves its distribution into the brain while maintaining distribution to peripheral tissues. Here we show that chronic systemic administration of ETV:IDS in a mouse model of MPS II reduced levels of peripheral and central nervous system GAGs, microgliosis, and neurofilament light chain, a biomarker of neuronal injury. Additionally, ETV:IDS rescued auricular and skeletal abnormalities when introduced in adult MPS II mice. These effects were accompanied by improvements in several neurobehavioral domains, including motor skills, sensorimotor gating, and learning and memory. Together, these results highlight the therapeutic potential of ETV:IDS for treating peripheral and central abnormalities in MPS II. DNL310, an investigational ETV:IDS molecule, is currently in clinical trials as a potential treatment for patients with MPS II.

项与 Tividenofusp alfa 相关的新闻（医药）

2025-12-08

·GlobeNewswire-Health Care

Denali Therapeutics and Royalty Pharma Announce $275 Million Royalty Funding Agreement

Dec. 04, 2025 -- Denali Therapeutics Inc. (Nasdaq: DNLI) and Royalty Pharma plc (Nasdaq: RPRX) today announced a $275 million synthetic royalty funding agreement based on future net sales of tividenofusp alfa. Tividenofusp alfa is Denali’s lead investigational TransportVehicle™-enabled enzyme replacement therapy for the treatment of mucopolysaccharidosis type II (MPS II, or Hunter syndrome). A Biologics License Application (BLA) for accelerated approval of tividenofusp alfa is under review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target date of April 5, 2026. “We are pleased to partner with Royalty Pharma, whose investment recognizes the value and potential of tividenofusp alfa for the Hunter community and supports our ability more broadly to realize the promise of the TransportVehicle platform,” said Ryan Watts, Ph.D., Chief Executive Officer of Denali Therapeutics. “With these additional funds, we are well positioned to advance our development programs as we prepare for the launch of tividenofusp alfa, unlocking broad opportunities across serious diseases.” “We are delighted to partner with Denali and acquire a royalty on tividenofusp alfa, an innovative therapy that addresses a significant unmet need in the cognitive and physical manifestations of Hunter syndrome,” said Pablo Legorreta, Chief Executive Officer and Chairman of the Board of Royalty Pharma. “Denali’s technology platform delivers therapeutics across the blood-brain barrier and is a promising new approach to brain diseases. We are thrilled to establish a relationship with Denali and believe tividenofusp alfa is a potential practice-changing therapy that could transform the lives of patients with Hunter syndrome.” The transaction is subject to various closing conditions, including Denali achieving U.S. FDA accelerated approval of tividenofusp alfa. At the closing, Royalty Pharma will make an initial payment of $200 million and Royalty Pharma will be obligated to make an additional payment of $75 million upon achieving European Medicines Agency (EMA) approval of tividenofusp alfa by December 31, 2029. In exchange, Royalty Pharma will receive a 9.25% royalty on worldwide net sales of tividenofusp alfa from Denali. The royalty payments to Royalty Pharma will cease upon reaching a multiple of 3.0x, or 2.5x if achieved by the first quarter of 2039. Denali Therapeutics Inc. is a biotechnology company pioneering a new class of biotherapeutics designed to cross the blood-brain barrier using its proprietary TransportVehicle™ platform. With a clinically validated delivery platform and a growing portfolio of therapeutic candidates across all stages of development, Denali is advancing toward its goal of delivering effective medicines to transform the lives of people living with neurodegenerative, lysosomal storage and other serious diseases. Founded in 1996, Royalty Pharma is the largest buyer of biopharmaceutical royalties and a leading funder of innovation across the biopharmaceutical industry, collaborating with innovators from academic institutions, research hospitals and non-profits through small and mid-cap biotechnology companies to leading global pharmaceutical companies. Royalty Pharma has assembled a portfolio of royalties which entitles it to payments based directly on the top-line sales of many of the industry’s leading therapies. Royalty Pharma funds innovation in the biopharmaceutical industry both directly and indirectly – directly when it partners with companies to co-fund late-stage clinical trials and new product launches in exchange for future royalties, and indirectly when it acquires existing royalties from the original innovators. Royalty Pharma’s current portfolio includes royalties on more than 35 commercial products, including Vertex’s Trikafta and Alyftrek, GSK’s Trelegy, Roche’s Evrysdi, Johnson & Johnson’s Tremfya, Biogen’s Tysabri and Spinraza, Servier’s Voranigo, AbbVie and Johnson & Johnson’s Imbruvica, Astellas and Pfizer’s Xtandi, Pfizer’s Nurtec ODT, and Gilead’s Trodelvy, and 18 development-stage product candidates. The content above comes from the network. if any infringement, please contact us to modify.

2025-12-05

·BioPharmaDive

Praxis soars higher; Bristol Myers’ CAR-T therapy wins broader use

Today, a brief rundown of news from Praxis Precision Medicines and Bristol Myers Squibb, as well as updates from Denali Therapeutics, Crescent Biopharma and AstraZeneca that you may have missed.Shares of Praxis Precision Medicines surged roughly 40% Friday, on news the company and the Food and Drug Administration are aligned on what should be included in an approval application for an experimental medicine known as ulixacaltamide. Praxis now expects to file for approval early next year. A longshot bet on this medicine began to pay off in October, when Praxis disclosed that two late-stage studies testing it against essential tremor had hit their main goals. The companys stock price more than tripled after the announcement, cresting around $200. Praxis also said Friday it stopped early, for overwhelming efficacy, a study of a different drug being tested in types of childhood encephalopathies. Shares traded at $266 apiece mid-Friday morning. Jacob Bell The FDA has broadened use of Bristol Myers Squibb's Breyanzi, clearing it on Thursday for use treating certain relapsed or refractory cases of marginal zone lymphoma. The new approval makes Breyanzi the first cell therapy available for the rare, slow-growing lymphatic tumor, which is believed to account for about 7% of all B-cell non-Hodgkin lymphoma cases, according ot the FDA. It's also the fifth different indication for Breyanzi, a cellular medicine Bristol Myers inherited through its acquisition of Celgene. Breyanzi generated $747 million in sales in 2024 and $966 million over the first nine months of 2025. Ben FidlerDenali Therapeutics may receive up to $275 million through a new deal that revolves around the companys most advanced drug. Known scientifically as tividenofusp alfa, the medicine is currently under FDA review, with an approval deadline of April 5. Denali has now agreed to pay a 9.25% royalty on worldwide net sales of tividenofusp alfa to Royalty Pharma. In exchange, Royalty will hand over $200 million up front, plus another $75 million if the treatment gets cleared for use in the European Union by the end of the decade. The agreement still hinges on Denalis drug securing U.S. approval. Additionally, the royalty payments would stop if the earnings reach either a 3-times multiple, or a 2.5-times multiple by the first quarter of 2039. Jacob BellCrescent Biopharma and China-based Kelun Biotech have formed an alliance that will see the two companies acquire partial rights to each others' cancer drugs and test them in combinations. Through the deal, Crescent has granted Kelun rights in Greater China to an experimental cancer immunotherapy targeting the proteins PD-1 and VEGF. Kelun, meanwhile, will hand Crescent most rights outside of Greater China to an experimental antibody-drug conjugate aimed at a target known as integrin beta-6. Both medicines are being developed for solid tumors and are in preclinical testing, with human studies expected to begin next year. Kelun will receive $80 million upfront from Crescent, while Crescent will pocket $20 million. Ben FidlerNeurimmune broadened an existing partnership with AstraZeneca, agreeing on Thursday to license to the British drugmaker rights to a preclinical prospect for amyloid light chain or AL amyloidosis. The Swiss biotech will receive an undisclosed upfront payment and is eligible for as much as $780 million in future payouts, should the therapy hit a series of development, regulatory and sales targets. Neurimmune and AstraZeneca first joined forces in 2022 to develop a treatment for transthyretin amyloidosis cardiomyopathy. That drug is now in late-stage testing. Ben Fidler '

上市批准免疫疗法引进/卖出细胞疗法并购

2025-12-04

·FierceBiotech

Royalty pens $275M financing deal for Denali drug awaiting delayed FDA decision

Royalty Pharma penned similar financing deals this year with Biogen, Zenas BioPharma and Revolution Medicines.\n While Denali Therapeutics awaits a delayed FDA decision on its Hunter syndrome drug, the biotech is already banking on the therapy’s commercial success.The agency had originally been due to make an approval call for the enzyme replacement therapy, called tividenofusp alfa, in early January 2026. But the FDA recently pushed back the decision date by three months.While Denali waits for the regulator’s verdict in April, the biotech is busy leveraging the potential sales tividenofusp alfa could bring in. This morning’s deal with Royalty Pharma, a buyer of biopharmaceutical royalties, will give Denali access to $200 million if the drug secures FDA approval, with an additional $75 million to follow if the therapy gets the green light in Europe.In return, Royalty will receive a 9.25% royalty on worldwide sales of tividenofusp alfa from Denali until it reaches three times the amount Royalty has handed to Denali—or, alternatively, 2.5 times the amount if the target is achieved by the first quarter of 2039.“We are delighted to partner with Denali and acquire a royalty on tividenofusp alfa, an innovative therapy that addresses a significant unmet need in the cognitive and physical manifestations of Hunter syndrome,” Royalty’s CEO and founder Pablo Legorreta said in the release.“Denali’s technology platform delivers therapeutics across the blood-brain barrier and is a promising new approach to brain diseases,” Legorreta added. “We are thrilled to establish a relationship with Denali and believe tividenofusp alfa is a potential practice-changing therapy that could transform the lives of patients with Hunter syndrome.” Royalty has penned similar financing deals so far this year, helping Biogen bankroll phase 3 development of its lupus candidate litifilimab, allowing Zenas BioPharma to complete work on its autoimmune candidate obexelimab and supporting Revolution Medicines in commercializing its lung cancer drug daraxonrasib.Denali already had almost $873 million in the bank at the end of September. CEO Ryan Watts, Ph.D., said the additional funds from Royalty would ensure the biotech was “well positioned to advance our development programs as we prepare for the launch of tividenofusp alfa, unlocking broad opportunities across serious diseases.”Tividenofusp alfa is a version of the iduronate 2-sulfatase enzyme that is engineered to penetrate the blood-brain barrier by binding to transferrin receptor 1, which normally shuttles iron into the brain.When Denali revealed the three-month delay to the FDA’s decision date back in October, the company put the move in the context of the updated clinical pharmacology information it had supplied to the FDA as part of the application review process. While Denali said this information was not related to the drug’s efficacy, safety or biomarkers, and did not involve supplying any additional clinical data, the FDA classified the submission as a major amendment to the application, which requires a three-month extension to the deadline.Hunter syndrome, also called mucopolysaccharidosis type II (MPS II), is characterized by patients\' inability to break down certain sugars, which leads to tissue and organ damage that ultimately causes stiff joints, delayed growth and enlarged spleens and livers, among other symptoms. The disease can also lead to cognitive and behavioral problems, and, in severe cases, patients may not survive beyond their teenage years.There is one approved enzyme replacement therapy for Hunter syndrome in Takeda’s Elaprase, which the Japanese drugmaker secured as part of its acquisition of Shire Pharmaceuticals in 2019.In August, the FDA pushed back the approval decision deadline for another Hunter syndrome treatment in the form of Regenxbio’s gene therapy clemidsogene lanparvovec after requesting additional data.

并购临床3期

100 项与 Tividenofusp alfa 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
黏多醣贮积症II型	申请上市	美国	Denali Therapeutics, Inc.	2025-04-02

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04251026 (DNLI-E-0002, PipelineReview) 人工标引	临床1/2期	黏多醣贮积症II型	47	tividenofusp alfa	鏇鹽壓衊鹽糧遞壓襯餘(鹽範簾憲窪積鹹繭襯構) = including infusion-related reactions (IRRs), anemia, vomiting, pyrexia, respiratory infections, and rash. 遞齋艱願襯淵淵憲繭鏇 (夢齋積積範夢顧蓋糧壓 )	积极	2025-02-06
Phase 1/2 Study (SSIEM2022)	临床1/2期	黏多醣贮积症II型	21	DNL310	艱網齋選醖憲構鹽齋簾(鹽網鹽壓膚糧齋選糧範) = 廠夢製夢鹹糧糧廠壓製築獵夢糧憲觸餘壓鬱壓 (鬱鏇觸顧艱遞齋鬱廠醖 ) 更多	积极	2022-08-30
SSIEM2022	临床1/2期	黏多醣贮积症II型	26	DNL310	鑰鏇願壓獵遞選選遞遞(鹹積糧憲鑰艱遞憲憲觸) = infusion-related reactions (IRRs) occurred in 20/26 (76.9%) participants during the 24-week study, and 2/14 (14%) participants during the first 6 months of the SE 繭觸鹽糧範鹽襯築積鑰 (膚繭鹽醖蓋獵遞築顧網 ) 更多	-	2022-08-30