givosiran 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
small interfering RNA including siRNA, miRNA and piRNA	5354	1639325-43-1

Description:

Molecule	Description
Synonyms: givosiran givosiran sodium ALN-AS1 givlaari	Givosiran is a double-stranded small interfering RNA that causes degradation of aminolevulinate synthase1 (ALAS1) mRNA in hepatocytes through RNA interference, reducing the elevated levels of liver ALAS1 mRNA. This leads to reduced circulating levels of neurotoxic intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG), factors associated with attacks and other disease manifestations of AHP. Molecular weight: Formula: CLOGP: LIPINSKI: None HAC: None HDO: None TPSA: ALOGS: ROTB: None

Molecule

Description

Synonyms:

givosiran
givosiran sodium
ALN-AS1
givlaari

Givosiran is a double-stranded small interfering RNA that causes degradation of aminolevulinate synthase1 (ALAS1) mRNA in hepatocytes through RNA interference, reducing the elevated levels of liver ALAS1 mRNA. This leads to reduced circulating levels of neurotoxic intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG), factors associated with attacks and other disease manifestations of AHP.

Molecular weight:
Formula:
CLOGP:
LIPINSKI: None
HAC: None
HDO: None
TPSA:
ALOGS:
ROTB: None

Drug dosage:

None

ADMET properties:

Property	Value	Reference
S (Water solubility)	357 mg/mL	Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Bocci G, Oprea TI, Benet LZ

Approvals:

Date	Agency	Company
March 2, 2020	EMA	Alnylam Netherlands B.V.
Nov. 20, 2019	FDA	ALNYLAM PHARMS INC
June 23, 2021	PMDA	ALNYLAM JAPAN K.K

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

None

FDA Adverse Event Reporting System (Geriatric)

None

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	A16AX16	ALIMENTARY TRACT AND METABOLISM OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS Various alimentary tract and metabolism products
FDA CS	M0406100	RNA, Small Interfering
FDA PE	N0000008852	Decreased RNA Integrity
FDA EPC	N0000193848	Small Interfering RNA
FDA EPC	N0000194024	Aminolevulinate Synthase 1-directed RNA Interaction

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Hepatic porphyria	indication	55056006	DOID:3133

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
EQ 189MG BASE/ML (EQ 189MG BASE/ML)	GIVLAARI	ALNYLAM PHARMS INC	N212194	Nov. 20, 2019	RX	SOLUTION	SUBCUTANEOUS	9708610	Jan. 1, 2024	TREATMENT OF ACUTE HEPATIC PORPHYRIA
EQ 189MG BASE/ML (EQ 189MG BASE/ML)	GIVLAARI	ALNYLAM PHARMS INC	N212194	Nov. 20, 2019	RX	SOLUTION	SUBCUTANEOUS	10131907	Aug. 24, 2028	TREATMENT OF ACUTE HEPATIC PORPHYRIA
EQ 189MG BASE/ML (EQ 189MG BASE/ML)	GIVLAARI	ALNYLAM PHARMS INC	N212194	Nov. 20, 2019	RX	SOLUTION	SUBCUTANEOUS	8828956	Dec. 4, 2028	TREATMENT OF ACUTE HEPATIC PORPHYRIA
EQ 189MG BASE/ML (EQ 189MG BASE/ML)	GIVLAARI	ALNYLAM PHARMS INC	N212194	Nov. 20, 2019	RX	SOLUTION	SUBCUTANEOUS	8106022	Dec. 12, 2029	TREATMENT OF ACUTE HEPATIC PORPHYRIA
EQ 189MG BASE/ML (EQ 189MG BASE/ML)	GIVLAARI	ALNYLAM PHARMS INC	N212194	Nov. 20, 2019	RX	SOLUTION	SUBCUTANEOUS	10125364	March 15, 2033	TREATMENT OF ACUTE HEPATIC PORPHYRIA
EQ 189MG BASE/ML (EQ 189MG BASE/ML)	GIVLAARI	ALNYLAM PHARMS INC	N212194	Nov. 20, 2019	RX	SOLUTION	SUBCUTANEOUS	9631193	March 15, 2033	TREATMENT OF ACUTE HEPATIC PORPHYRIA
EQ 189MG BASE/ML (EQ 189MG BASE/ML)	GIVLAARI	ALNYLAM PHARMS INC	N212194	Nov. 20, 2019	RX	SOLUTION	SUBCUTANEOUS	9133461	Nov. 30, 2033	TREATMENT OF ACUTE HEPATIC PORPHYRIA
EQ 189MG BASE/ML (EQ 189MG BASE/ML)	GIVLAARI	ALNYLAM PHARMS INC	N212194	Nov. 20, 2019	RX	SOLUTION	SUBCUTANEOUS	10119143	Oct. 3, 2034	TREATMENT OF ACUTE HEPATIC PORPHYRIA
EQ 189MG BASE/ML (EQ 189MG BASE/ML)	GIVLAARI	ALNYLAM PHARMS INC	N212194	Nov. 20, 2019	RX	SOLUTION	SUBCUTANEOUS	11028392	Oct. 3, 2034	TREATMENT OF ACUTE HEPATIC PORPHYRIA

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
EQ 189MG BASE/ML (EQ 189MG BASE/ML)	GIVLAARI	ALNYLAM PHARMS INC	N212194	Nov. 20, 2019	RX	SOLUTION	SUBCUTANEOUS	Nov. 20, 2024	NEW CHEMICAL ENTITY
EQ 189MG BASE/ML (EQ 189MG BASE/ML)	GIVLAARI	ALNYLAM PHARMS INC	N212194	Nov. 20, 2019	RX	SOLUTION	SUBCUTANEOUS	Nov. 20, 2026	INDICATED FOR THE TREATMENT OF ADULTS WITH ACUTE HEPATIC PORPHYRIA (AHP)

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
aminolevulinate synthase1 (ALAS1) mRNA	RNA	P13196	HEM1_HUMAN	ANTISENSE INHIBITOR				UNKNOWN	DRUG LABEL

External reference:

ID	Source
ROV204583W	UNII
C4688584	UMLSCUI
CHEMBL4297760	ChEMBL_ID
156323004	PUBCHEM_CID
DB15066	DRUGBANK_ID
CHEMBL4594265	ChEMBL_ID
D11702	KEGG_DRUG
10280	INN_ID
018210	NDDF
018211	NDDF
1217169003	SNOMEDCT_US
830100005	SNOMEDCT_US
830239005	SNOMEDCT_US
4038984	VANDF
2265712	RXNORM
327500	MMSL
37780	MMSL
d09456	MMSL
C000630124	MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
GIVLAARI	HUMAN PRESCRIPTION DRUG LABEL	1	71336-1001	INJECTION, SOLUTION	189 mg	SUBCUTANEOUS	NDA	28 sections
GIVLAARI	HUMAN PRESCRIPTION DRUG LABEL	1	71336-1001	INJECTION, SOLUTION	189 mg	SUBCUTANEOUS	NDA	28 sections
GIVLAARI	HUMAN PRESCRIPTION DRUG LABEL	1	71336-1001	INJECTION, SOLUTION	189 mg	SUBCUTANEOUS	NDA	28 sections