Idursulfase

SOUTH SAN FRANCISCO, CA, USA I July 07, 2025 I Denali Therapeutics Inc. (Nasdaq: DNLI) today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) seeking accelerated approval for tividenofusp alfa for the treatment of Hunter syndrome (mucopolysaccharidoses type II, or MPS II), a rare and progressive genetic disorder. The FDA granted the BLA Priority Review with a Prescription Drug User Fee Act (PDUFA) target action date of January 5, 2026. Hunter syndrome is caused by a deficiency in the iduronate 2-sulfatase (IDS) enzyme, which is needed to break down complex sugars called glycosaminoglycans that build up in the brain and body, starting at a young age. Current therapies do not cross the blood-brain barrier and lack the potential to address the impact of the disease on cognitive abilities and behavior. Tividenofusp alfa is an investigational, next-generation enzyme replacement therapy composed of IDS fused to Denali’s TransportVehicle™ platform and is designed to deliver IDS into the brain and the body, aiming to treat neurological manifestations of the disease in addition to physical symptoms. “We are grateful to the FDA for their recognition of the urgent need for new therapies that could offer a significant improvement in the treatment of Hunter syndrome, as reflected by their priority review designation for our Biologics License Application for tividenofusp alfa,” said Carole Ho, M.D., Chief Medical Officer and Head of Development of Denali Therapeutics. “If FDA-approved, tividenofusp alfa would mark the first significant advancement in nearly two decades for enzyme replacement therapy for individuals living with Hunter syndrome because of its potential for delivery to tissues throughout the brain and the body. This is also a pivotal milestone for our TransportVehicle platform, which continues to progress with the aim of treating a wide range of lysosomal storage diseases and neurodegenerative disorders.” The BLA submission is supported by data from the open-label, single-arm Phase 1/2 study of tividenofusp alfa in 47 participants with Hunter syndrome. Denali continues to prepare for a potential commercial launch in the U.S. and is conducting the ongoing Phase 2/3 COMPASS study to support global regulatory approvals. 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 the Denali TransportVehicle ™ Platform The blood-brain barrier (BBB) is essential in maintaining the brain’s microenvironment and protecting it from harmful substances and pathogens circulating in the bloodstream. Historically, the BBB has posed significant challenges to drug development for central nervous system diseases by preventing most drugs from reaching the brain in therapeutically relevant concentrations. Denali’s TransportVehicle™ (TV) platform is a proprietary technology designed to effectively deliver large therapeutic molecules such as antibodies, enzymes, proteins, and oligonucleotides across the BBB after intravenous administration. The TV platform is based on engineered Fc domains that bind to specific natural transport receptors, such as transferrin receptor and CD98 heavy chain amino acid transporter, which are expressed at the BBB and deliver the TV and its therapeutic cargo to the brain through receptor-mediated transcytosis. In animal models, antibodies and enzymes engineered with the TV platform demonstrate more than 10- to 30-fold greater brain exposure than similar antibodies and enzymes without this technology. Oligonucleotides engineered with the TV platform demonstrate more than a 1,000-fold greater brain exposure in primates than systemically delivered oligonucleotides without this technology. Improved exposure and broad distribution in the brain may increase therapeutic efficacy by enabling widespread achievement of therapeutically relevant concentrations of product candidates. The TV platform has been clinically validated and three TV-enabled programs are currently in clinical development. 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 . SOURCE: Denali Therapeutics

Lysosomal storage disorder R&D is racing beyond enzyme infusions to gene and chaperone therapies, aiming for brain access, wider reach and better value. LSDs prove that ‘rare’ does not mean small. The companies that marry CNS penetration with global affordability will own the next chapter of lysosomal medicine.” — DataM Intelligence AUSTIN, TX, UNITED STATES, June 5, 2025 / EINPresswire.com / -- Lysosomal Storage Disorders: Drafting the Next Chapter in Rare-Disease Innovation Lysosomal storage disorders (LSDs) sit at the intersection of genetics, neurology and high-stakes drug development. Individually they affect only a few births per hundred-thousand, yet collectively they represent a portfolio of roughly seventy ultra-rare diseases-all triggered by faulty genes that leave one crucial lysosomal enzyme missing, broken or misrouted. The result is a slow, relentless build-up of cellular waste that damages every organ it touches, often including the brain. Three decades ago the field barely existed; now it is a $10.4 billion global market growing at about ten percent a year. Enzyme-replacement infusions, once regarded as miracle treatments, are giving way to slimmer small molecules, oral substrate reducers and one-and-done gene therapies. For industry strategists, payers and patient groups, the coming decade will hinge on who can break through four stubborn barriers: brain delivery, early diagnosis, lifelong affordability and truly curative potential. Book Your Free CI Consultation Call: https://www.datamintelligence.com/strategic-insights/ci/lysosomal-storage-diseases-lsds A Quick Primer-Why LSDs Are So Hard to Treat Because lysosomes sit inside nearly every cell, and because many LSDs begin their damage in utero, timing is everything. By the time classic symptoms appear-enlarged liver and spleen, skeletal deformities, loss of developmental milestones-irreversible harm is often under way. The current standard of care follows three paths: Enzyme Replacement Therapy (ERT): Regular IV infusions supply the missing enzyme but cannot cross the blood–brain barrier. They are expensive, time-consuming and lifelong. Substrate Reduction Therapy (SRT): Small molecules dial down production of the toxic substrate, easing the burden on deficient enzymes. SRTs are oral and convenient but often mutation-specific. Gene Therapy: Still early but accelerating, viral vectors (or ex vivo modified stem cells) add a functional copy of the gene, aiming for a single-dose solution. High cost, immune reactions and manufacturing scale remain obstacles. Between those options lives a patchwork of chaperone drugs, newborn-screening pilots and experimental intrathecal enzyme infusions-all signs of a field that knows what it wants but hasn’t yet nailed the execution. Market Leaders, Challengers and the Innovation Game Sanofi/Genzyme remains the heavyweight, with marquee franchises in Gaucher (Cerezyme), Fabry (Fabrazyme) and Pompe disease (Myozyme, Nexviazyme). Its global footprint, manufacturing depth and payer muscle keep it in pole position-but also expose it to pricing scrutiny and biosimilar erosion as patents wane. Takeda follows with Elaprase for Hunter syndrome, Vpriv for Gaucher and Replagal for Fabry. Its strategy hinges on service hubs in emerging markets and bundling support programs with therapy. BioMarin has carved out the ultra-rare end of the spectrum: CLN2 brain-directed enzyme Brineura and MPS programs Aldurazyme and Naglazyme. Investors view BioMarin as the bellwether for whether CNS delivery can justify premium pricing. Amicus Therapeutics leads the pharmacological-chaperone niche with Galafold for amenable Fabry mutations and is pushing AT-GAA, a two-part therapy for Pompe, through regulatory review. Ultragenyx and Orchard Therapeutics headline the gene-therapy vanguard-Ultragenyx with AAV programs in Sanfilippo and metabolic diseases, Orchard with Libmeldy, an autologous stem-cell gene therapy that offers presymptomatic children with metachromatic leukodystrophy the promise of near-normal development. Behind them, a second wave of biotech names-Avrobio, Passage Bio, Prevail, and a roster of CRISPR and lipid-nanoparticle start-ups-are vying to extend gene-delivery reach, reduce immune barriers and slash manufacturing cost by orders of magnitude. Where the Gaps Still Hurt 1. Early Diagnosis. Symptoms are vague, newborn screens limited and next-generation sequencing still expensive in lower-income regions. Every month of delay can mean lost neurons. AI-based pattern recognition of electronic health records and drop-of-blood enzyme assays could change the timeline. 2. Brain-First Diseases. Krabbe, Tay–Sachs and neuronopathic Gaucher progress rapidly because today’s IV enzymes cannot reach the central nervous system. Companies are testing intrathecal catheters, receptor-mediated transport tags and stem-cell gene therapies, but large-scale proof is pending. 3. Treatment Burden. Weekly or bi-weekly hospital infusions strain families and health systems alike. Oral SRTs and sub-cutaneous enzymes (under review) promise home dosing. 4. Affordability. Sticker prices north of $300 000 per year are routine for ERT, while gene therapies launch in the $2–3 million range. Value-based contracts, outcomes guarantees and regional tiered pricing are emerging but patchwork. 5. Global Access. Only a fraction of patients in Latin America, Africa and parts of Asia receive formal diagnosis, let alone therapy. Companies that invest early in local manufacturing or partner with NGOs can build brand equity and future market share simultaneously. The Target Opportunity Profile-What an “Ideal” LSD Therapy Looks Like in 2025 + A winning next-generation therapy would check five boxes: - Mutation-Agnostic Reach: One product that covers the majority of variants in a given disease, avoiding the fragmentation that plagues exon-specific approaches. - CNS Penetration: Whether via receptor-targeted enzymes, intrathecal gene therapy or re-engineered AAV capsids, future blockbusters must show measurable impact on neurocognitive decline. - Single-Dose or Low-Burden Dosing: Families and payers are eager to trade weekly infusions for a once-monthly sub-cutaneous shot-or, ideally, a one-time gene correction. - Favorable Safety and Immune Profile: Manageable liver signals, minimal complement activation and a re-dosing pathway if immunity develops. - Scalable Economics: A path to sub-$1 million pricing for one-time therapies, enabled by high-yield vector production and lean distribution models. Developers who bring three out of those five to market-backed by strong newborn-screening advocacy-will command premium reimbursement and faster adoption. Market Forecast: Steady Double-Digit Growth, but Not Without Hurdles DataM Intelligence projects the lysosomal-disease therapeutics market could cross $25 billion by 2033, assuming at least four new gene or chaperone therapies win global approval, penetration expands in Asia-Pacific, and payers accept outcomes-based pricing. Headwinds include vector-manufacturing capacity, regulator caution after safety signals in systemic AAV trials, and potential backlash against high launch prices. Still, with a 10 percent compound growth trajectory, LSDs remain one of the most attractive segments in rare-disease pharma. Download Free CI Sample Report: https://www.datamintelligence.com/strategic-insights/sample/lysosomal-storage-diseases-lsds Why Competitive Intelligence Matters More Than Ever In a field where each product addresses a fraction of an already tiny population, timing and differentiation are life-or-death matters-both for patients and companies. Our latest LSD Competitive Intelligence Report combines real-time clinical-trial analytics, KOL sentiment, and payer-access tracking to help executives: - Spot white-space indications before rivals do. - Benchmark trial designs and biomarker strategies against the front-runners. - Model pricing and reimbursement under multiple policy scenarios. - Identify acquisition or licensing targets early, when valuations are still rational. Read More CI Report: 1. Friedreichs Ataxia Disease Modifying Therapies Market Intelligence 2. Cell and Gene Therapy | Competitive Intelligence Sai Kumar DataM Intelligence 4market Research LLP +1 877-441-4866 sai.k@datamintelligence.com Visit us on social media: LinkedIn X Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.