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Tofersen

Phase 3

Amyotrophic Lateral Sclerosis Associated With a SOD1 Gene Mutation | Small molecule | Neurology |Biogen Inc.|Last Updated: Mar 30, 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-BlindNO_TREATMENT_CONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment158
FDA Designations
PRIORITY_REVIEW
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT04856982A Study of BIIB067 (Tofersen) Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 MutationPHASE3 ACTIVE NOT_RECRUITING 158May 17, 2021Apr 30, 2028Mar 30, 202632 United States, Australia +12
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Study Endpoints
Primary Endpoints
Parts B and C: Percentage of Participants with Emergence of Clinically Manifest ALS Within 24 Months of Part B Baseline
Up to 24 months
Secondary Endpoints
Parts B and C: Time to Emergence of Clinically Manifest ALS
Up to 5.6 years
Parts B and C: Change in ALS Functional Rating Scale (ALSFRS-R) Total Score
Up to 5.6 years
Parts B and C: Change from Baseline in Percent Predicted Slow Vital Capacity (SVC)
Up to 5.6 years
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Study Design & Arms
AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Part A: Natural History Run-inNO_INTERVENTIONParticipants enrolled in Part A will undergo blood draws approximately once every 28 days to assess neurofilament light chain (NfL) levels.
Part B: Randomized, Double-Blind, Placebo-ControlledEXPERIMENTALParticipants from Part A who meet the protocol-defined NfL threshold and remain presymptomatic may be eligible to participate in Part B. During Part B, participants will receive tofersen 100 milligram (mg) or placebo via intrathecal (IT) injection on Days 1, 15, 29, and every 28 days thereafter for up to approximately 5.6 years.
Part C: Open-Label ExtensionEXPERIMENTALParticipants from Part B who develop clinically manifest ALS may be eligible to participate in Part C. During Part C, participants who received placebo in Part B will receive tofersen 100 mg via IT injection on Days 1, 15, 29, and every 28 days thereafter up to the final maintenance dost visit. Participants who received tofersen during Part B will receive tofersen 100 mg on Days 1, 29, and every 28 days thereafter up to the final maintenance dost visit, with a dose of placebo on Day 15 to maintain the study blind. The combined duration of Part B and Part C is up to approximately 5.6 years.
Part D: Open-Label TreatmentEXPERIMENTALParticipants from Part A who develop clinically manifest ALS prior to randomization in Part B may be eligible to participate in Part D. During Part D, participants will receive tofersen100 mg via IT injection on Days 1, 15, 29, and every 28 days thereafter for up to 2 years.
Interventions
NameTypeDescription
TofersenDRUGAdministered as specified in the treatment arm
PlaceboDRUGAdministered as specified in the treatment arm
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites32

Key Part A Inclusion Criteria: * Participants should have a protocol-defined rapidly progressive SOD1 mutation, confirmed by a central reader, or a SOD1 mutation that is approved for inclusion by an external mutation adjudication committee. * Participants with plasma NfL level less than the protoco...

Countries:United StatesAustraliaBelgiumBrazilCanadaFranceGermanyItalyJapanPolandSouth KoreaSpainSwedenUnited Kingdom
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Recent Changes (Last 90 Days)
MEDIUMMay 26, 2026NCT04856982primaryCompletionDate: changed
LOWMay 24, 2026NCT04856982studyFirstPostDate: changed