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tividenofusp alfa

Phase 2

Mucopolysaccharidosis II | Small molecule | Rare Disease |Denali Therapeutics Inc.|Last Updated: Jun 11, 2026

Success Probability

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMC
Total Trials3
Total Enrollment209

FDA Designations

PRIORITY_REVIEWBREAKTHROUGH_THERAPYORPHAN_DRUGFAST_TRACKRARE_PEDIATRIC_DISEASE

Clinical trial landscape

tividenofusp alfa · 3 trials · 1 indication

Phase 2 2Phase 1 1
NCT06075537An Extension Study of the Long-Term Safety, Tolerability, and Efficacy of Tividenofusp Alfa (DNL310) in Participants With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007Mucopolysaccharidosis II
ENROLLING BY_INVITATION99 Analytics
NCT05371613A Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric and Young Adult Participants With Neuronopathic (nMPS II) or Non-Neuronopathic Mucopolysaccharidosis Type II (nnMPS II)Mucopolysaccharidosis II
RECRUITING63 Analytics
PHASE2ENROLLING BY_INVITATION
An Extension Study of the Long-Term Safety, Tolerability, and Efficacy of Tividenofusp Alfa (DNL310) in Participants With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007
Mucopolysaccharidosis IIUnlock trial analytics
PHASE2RECRUITING
A Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric and Young Adult Participants With Neuronopathic (nMPS II) or Non-Neuronopathic Mucopolysaccharidosis Type II (nnMPS II)
Mucopolysaccharidosis IIUnlock trial analytics

Study Endpoints

Primary Endpoints

Incidence and intensity of treatment-emergent adverse events (TEAEs)
5 years
Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period
5 years
Incidence and intensity of infusion-related reactions (IRRs)
5 years

The intensity of IRRs will be assessed following each infusion of DNL310 using the categories of Mild, Moderate and Severe. IRRs will be summarized overall as well as stratified by intensity.

Percent change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A)
24 weeks
Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A)
96 weeks
Incidence and severity of treatment-emergent adverse events (TEAEs)
24 weeks, 104 weeks, and 357 weeks
Change from baseline in urine total glycosaminoglycan (GAG) concentrations
24 weeks, 104 weeks, and 357 weeks
Incidence and severity of infusion-related reactions (IRRs)
24 weeks, 104 weeks, and 357 weeks
Change from baseline in concomitant medications
24 weeks, 104 weeks, and 357 weeks

Secondary Endpoints

Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration
5 years
Change from baseline in the Vineland-3 Adaptive Behavior Scale
5 years
Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score
5 years
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Cohort A2EXPERIMENTALParticipants with nMPS II, aged ≥5 to ≤10 years
Cohort B2EXPERIMENTALParticipants with nMPS II or nnMPS II, aged ≥1 to ≤18 years
Cohort C2EXPERIMENTALParticipants with nMPS II, aged \<4 years
Cohort D2EXPERIMENTALParticipants with nMPS II or nnMPS II, aged ≤18 years with preexisting hepatomegaly who have never taken standard-of-care ERT
Cohort E2EXPERIMENTALParticipants with nMPS II, aged ≥6 years; participants with nnMPS II, aged \<6 or ≥17 years; or participants with nMPS II, aged ≥1 to ≤18 years, with a history of prior HSCT or gene therapy and have completed at least 48 weeks in Study DNLI-E-0001
Cohort A7EXPERIMENTALParticipants with nMPS II, aged ≥2 to \<6 years
Cohort B7EXPERIMENTALParticipants with nnMPS II, aged ≥6 to \<17 years
Cohort A: Participants with nMPS IIEXPERIMENTAL -
Cohort B: Participants with nnMPS IIEXPERIMENTAL -
Open-label Treatment PhaseEXPERIMENTALParticipants who meet pre-specified criteria may receive DNL310 or idursulfase
Cohort AEXPERIMENTALDose escalation followed by a consistent dose level in participants with neuronopathic MPS II
Cohort BEXPERIMENTALA consistent dose level in participants with non-neuronopathic MPS II, neuronopathic MPS II, or unknown phenotype followed by dose escalation in some participants.
Cohort CEXPERIMENTALA consistent dose level in participants with neuronopathic MPS II
Cohort DEXPERIMENTALA consistent dose level in participants with non-neuronopathic MPS II or neuronopathic MPS II
Cohort EEXPERIMENTALA consistent dose level in participants with non-neuronopathic MPS II or neuronopathic MPS II

Interventions

NameTypeDescription
tividenofusp alfaDRUGIntravenous repeating dose
idursulfaseDRUGIntravenous repeating dose
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Eligibility Criteria

Age RangeN/A to 18 Years
SexALL
Healthy VolunteersNo
Study Sites29

Key Inclusion Criteria: * For participants from Study DNLI-E-0002 only: Completed at least through the Week 49 visit in Study DNLI-E-0002 and did not discontinue study intervention early * For participants from Study DNLI-E-0007 only: Completed the treatment period of 96 weeks in Cohort A for nMPS ...

Countries:United StatesArgentinaBelgiumCanadaCzechiaFranceGermanyItalyNetherlandsSpainSwedenTurkey (Türkiye)United KingdomAustraliaBrazil
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Recent Changes (Last 90 Days)

LOWJun 11, 2026NCT06075537lastUpdatePostDate: changed
LOWJun 11, 2026NCT06075537lastUpdatePostDate: changed

Frequently asked questions about tividenofusp alfa

What is tividenofusp alfa used for?

Tividenofusp alfa is an investigational small molecule being developed for Mucopolysaccharidosis II, also known as Hunter syndrome. It is being studied in pediatric, young adult, and adult participants with both neuronopathic and non-neuronopathic forms of the disease. The drug is currently in Phase 2 clinical development.

Who makes tividenofusp alfa?

Tividenofusp alfa is being developed by Denali Therapeutics Inc., a biopharmaceutical company traded on the Nasdaq under the ticker symbol DNLI. The company is conducting multiple clinical trials of the drug in patients with Mucopolysaccharidosis II across numerous countries, including the United States, Canada, and several European nations.

What phase is tividenofusp alfa in?

Tividenofusp alfa is currently in Phase 2 clinical development. It has received several FDA designations, including Priority Review, Breakthrough Therapy, Orphan Drug, Fast Track, and Rare Pediatric Disease. The drug is investigational and has not been approved by the FDA, as it is still undergoing clinical trials.

What clinical trials is tividenofusp alfa in?

Tividenofusp alfa is being studied in three active clinical trials. NCT04251026 is a Phase 1 study in pediatric participants with Hunter syndrome. NCT05371613 is a Phase 2 study comparing tividenofusp alfa to idursulfase in pediatric and young adult participants. NCT06075537 is a Phase 2 extension study evaluating long-term safety and efficacy.

Is tividenofusp alfa the same as DNL310?

Yes, tividenofusp alfa is also known as DNL310. Clinical trial records refer to the drug by both names, with DNL310 appearing in study titles and tividenofusp alfa as the official nonproprietary name. Both names refer to the same investigational therapy for Mucopolysaccharidosis II.

How does tividenofusp alfa work?

Tividenofusp alfa is a small molecule designed to treat Mucopolysaccharidosis II. The drug is being evaluated for its ability to address the underlying enzyme deficiency associated with the condition. However, the specific molecular target of tividenofusp alfa has not been disclosed in the available clinical trial information.