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ION464

Phase 1

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

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDBiomarker
Total Trials1
Total Enrollment40
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT04165486Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ION464 Administered to Adults With Multiple System Atrophy (HORIZON)PHASE1 RECRUITING 40Jul 21, 2022Sep 1, 2027Apr 27, 202615 Austria, France +3
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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 — 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