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Fazisiran

Phase 2

Alpha 1-Antitrypsin Deficiency | Small molecule | Other |Arrowhead Pharmaceuticals, Inc.|Last Updated: Nov 4, 2025

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_CONTROLLEDDMC
Total Trials1
Total Enrollment40
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT03945292Safety, Tolerability and Pharmacodynamic Effect of Fazirsiran (TAK-999, ARO-AAT)PHASE2 COMPLETED 40Aug 7, 2019Sep 18, 2023Nov 4, 202521 United States, Germany +4
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Study Endpoints
Primary Endpoints
Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16
Baseline, Week 16 (+/- 2 weeks)
Secondary Endpoints
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase
Double Blind Phase (up to Week 48): dose administration through end of study (EOS) or Early Termination or first dose of open-label phase fazirsiran.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase
From dose administration of the first dose of open-label phase fazirsiran through EOS or Early Termination (up to Week 196).
Absolute Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis
Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks)
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Study Design & Arms
AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Fazirsiran 25 mg DB/200 mg OLEXPERIMENTALDouble-blind (DB) Period: Participants with no fibrosis: Administered on Day 1 and Week 4. Participants with fibrosis: Administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. Open-label (OL) Period: Participants with fibrosis at Screening who received double-blind (DB) fazirsiran 25 mg and who completed the post-dose liver biopsy at Week 48 (or Week 72 or Week 96) entered the open-label phase and received fazirsiran 200 mg every 12 weeks for the duration of the study.
Fazirsiran 100 mg DB/200 mg OLEXPERIMENTALDB Period: Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. OL Period: Participants with fibrosis at Screening who received double-blind (DB) fazirsiran 100 mg and who completed the post-dose liver biopsy at Week 48 (or Week 72 or Week 96) entered the open-label phase and received fazirsiran 200 mg every 12 weeks for the duration of the study.
Fazirsiran 200 mg DB/200 mg OLEXPERIMENTALDB Period: Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. OL Period: Participants with fibrosis at Screening who received double-blind (DB) fazirsiran 200 mg and who completed the post-dose liver biopsy at Week 48 (or Week 72 or Week 96) entered the open-label phase and received fazirsiran 200 mg every 12 weeks for the duration of the study
Placebo DB / Fazirsiran 200 mg OLPLACEBO_COMPARATORDB Period: Participants with no fibrosis: Placebo administered on Day 1 and Week 4. Participants with fibrosis: Placebo administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. OL Period: Participants with fibrosis at Screening who received double-blind (DB) placebo and who completed the post-dose liver biopsy at Week 48 (or Week 72 or Week 96) entered the open-label phase and received fazirsiran 200 mg every 12 weeks for the duration of the study.
Interventions
NameTypeDescription
Fazisiran InjectionDRUGsolution for subcutaneous (sc) injection
PlaceboOTHERsterile normal saline (0.9% NaCl), calculated to match active comparator, for sc injection
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Eligibility Criteria
Age Range18 Years — 75 Years
SexALL
Healthy VolunteersNo
Study Sites21

Inclusion Criteria: * Diagnosis of AATD * Liver biopsy at Screening indicating liver fibrosis (score less than F4); a patient with no fibrosis may participate based on a previous biopsy conducted within one year * Women of childbearing potential must have a negative pregnancy test, cannot be breast...

Countries:United StatesGermanyItalyNetherlandsPortugalSpain
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