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Givosiran

Phase 3

Acute Hepatic Porphyria | Small molecule | Gastrointestinal |Alnylam Pharmaceuticals, Inc.|Last Updated: Apr 22, 2024

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 Enrollment94
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT03338816ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP)PHASE3 COMPLETED 94Nov 16, 2017May 31, 2021Apr 22, 202436 United States, Australia +16
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Study Endpoints
Primary Endpoints
Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP)
6 months

Porphyria attacks were defined as meeting all of the following criteria: an acute episode of neurovisceral pain in the abdomen, back, chest, extremities and/or limbs, no other medically determined cause, and required treatment with intravenous (IV) dextrose or hemin, carbohydrates, or analgesics, or other medications such as antiemetics at a dose or frequency beyond the participant's usual daily porphyria management. The annualized rate of porphyria attacks is a composite endpoint which included porphyria attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home.

Secondary Endpoints
The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP
3 and 6 months
The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP
6 months
Annualized Rate of Hemin Administration in Participants With AIP
6 months
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Study Design & Arms
AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Givosiran/GivosiranEXPERIMENTALGivosiran 2.5 mg/kg administered subcutaneously (SC), monthly (QM), for 6 months during the 6-Month Double-blind (DB) Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the Open-label Extension (OLE) Period.
Placebo/GivosiranPLACEBO_COMPARATORMatching placebo (normal saline \[0.9% NaCl\]) was administered SC, QM, for 6 months during the 6-Month DB Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the OLE period.
Interventions
NameTypeDescription
GivosiranDRUGGivosiran by SC
PlaceboDRUGMatching placebo (normal saline \[0.9% NaCl\]) by SC
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Eligibility Criteria
Age Range12 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites36

Inclusion Criteria: * ≥ 12 years of age * Diagnosed with Acute Hepatic Porphyria (Acute Intermittent Porphyria, Hereditary Corproporhyria, Variegate Porphyria, aminolevulinic acid (ALA) dehydratase deficient porphyria) * Elevated urinary or plasma porphobilinogen (PBG) or ALA values within the past...

Countries:United StatesAustraliaBulgariaCanadaDenmarkFinlandFranceGermanyItalyJapanMexicoNetherlandsPolandSouth KoreaSpainSwedenTaiwanUnited Kingdom
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