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ION464

Phase 1

Multiple System Atrophy | Small molecule | Neurology |Ionis Pharmaceuticals, Inc.|Last Updated: Apr 27, 2026

Target and mechanism

Molecular targetSNCA
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials1
Total Enrollment40

FDA Designations

No designations recorded

Clinical trial landscape

ION464 · 1 trial · 1 indication

Phase 1 1
NCT04165486Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ION464 Administered to Adults With Multiple System Atrophy (HORIZON)Multiple System Atrophy
RECRUITING40 Analytics
PHASE1RECRUITING
Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ION464 Administered to Adults With Multiple System Atrophy (HORIZON)
Multiple System AtrophyUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Participants with Adverse Events (AEs)
Baseline up to approximately 36 weeks
Number of Participants with Serious Adverse Events (SAEs)
Baseline up to approximately 36 weeks

Secondary Endpoints

Change From Baseline in Cerebrospinal Fluid (CSF) Levels of Total alpha-synuclein (α-syn)
Baseline up to approximately 36 weeks
Serum Concentration of ION464
Baseline up to approximately 36 weeks
Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of ION464
Baseline up to approximately 36 weeks
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Study Design & Arms

AllocationRANDOMIZED
MaskingTRIPLE
ModelSEQUENTIAL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Part 1: ION464EXPERIMENTALION464 will be administered at multiple-ascending doses by IT injection at regular intervals over 12 weeks.
Part 1: PlaceboPLACEBO_COMPARATORION464-matching placebo will be administered by IT injection at regular intervals over 12 weeks.
Part 2: ION464EXPERIMENTALION464 will be administered at the same doses as Part 1 by IT injection, at regular intervals, for 72 weeks.
Part 2: PlaceboPLACEBO_COMPARATORION464-matching placebo will be administered by IT injection, at regular intervals, for 72 weeks.

Interventions

NameTypeDescription
ION464DRUGION464 will be administered by IT injection.
PlaceboDRUGION464-matching placebo will be administered by IT injection.
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Eligibility Criteria

Age Range40 Years to 70 Years
SexALL
Healthy VolunteersNo
Study Sites15

Key Inclusion Criteria: * Screening single-photon emission computed tomography (SPECT) with DaTscan™ (ioflupane I123 injection) results demonstrating loss (whether symmetric or asymmetric) of dopamine nerve terminals in the striatum consistent with neurodegenerative parkinsonism, as assessed with q...

Countries:AustriaFranceGermanyPortugalUnited Kingdom
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Recent Changes (Last 90 Days)

LOWMay 26, 2026NCT04165486primaryCompletionDate: changed
LOWMay 24, 2026NCT04165486studyFirstPostDate: changed

Frequently asked questions about ION464

What is ION464 used for in Multiple System Atrophy?

ION464 is an investigational small molecule being developed for the treatment of Multiple System Atrophy (MSA), a rare neurodegenerative disorder. It is currently in Phase 1 clinical development and has not been approved by regulatory authorities. The drug is being studied to evaluate its safety, tolerability, and pharmacokinetics in adults with MSA.

What does ION464 target?

ION464 targets SNCA, the gene that encodes the alpha-synuclein protein. Abnormal accumulation of alpha-synuclein is a hallmark of Multiple System Atrophy. By targeting SNCA, ION464 aims to address the underlying pathology of the disease, though its exact mechanism of action is still under investigation in clinical trials.

Who makes ION464?

ION464 is being developed by Ionis Pharmaceuticals, Inc., a biopharmaceutical company traded on NASDAQ under the ticker symbol IONS. Ionis is conducting a Phase 1 clinical trial to evaluate the drug's safety, tolerability, and pharmacokinetics in adults with Multiple System Atrophy.

What phase is ION464 in?

ION464 is in Phase 1 clinical development. It is an investigational drug and has not received regulatory approval. The ongoing Phase 1 trial is recruiting participants with Multiple System Atrophy to assess the drug's safety, tolerability, and how it is processed by the body.

What clinical trials is ION464 in?

ION464 is being studied in a Phase 1 clinical trial with the identifier NCT04165486, titled 'Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ION464 Administered to Adults With Multiple System Atrophy (HORIZON)'. The trial is recruiting 40 participants across Austria, France, Germany, Portugal, and the United Kingdom.

Is ION464 the same as other drugs for Multiple System Atrophy?

ION464 is a distinct investigational small molecule targeting SNCA, the gene for alpha-synuclein. It is not known to be the same as any other approved or investigational drug. Its development is specific to Multiple System Atrophy, and it is currently in Phase 1 trials to evaluate its safety and tolerability.