inclisiran 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
small interfering RNA including siRNA, miRNA and piRNA 5498 1639324-58-5

Description:

MoleculeDescription

Molfile

Synonyms:

  • inclisiran
  • leqvio
  • ALN-PCSsc
  • ALN-60212
  • KJX-839
  • PCSK9si
Inclisiran is a double-stranded small interfering ribonucleic acid (siRNA), conjugated on the sense strand with triantennary N-Acetylgalactosamine (GalNAc) to facilitate uptake by hepatocytes. In hepatocytes, inclisiran utilizes the RNA interference mechanism and directs catalytic breakdown of mRNA for PCSK9. This increases LDL-C receptor recycling and expression on the hepatocyte cell surface, which increases LDL-C uptake and lowers LDL-C levels in the circulation.
  • Molecular weight:
  • Formula:
  • CLOGP:
  • LIPINSKI: None
  • HAC: None
  • HDO: None
  • TPSA:
  • ALOGS:
  • ROTB: None

Drug dosage:

DoseUnitRoute
1.60 mg P

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

None

Approvals:

DateAgencyCompanyOrphan
Dec. 9, 2020 EMA Novartis Europharm Limited
Dec. 22, 2021 FDA NOVARTIS PHARMS CORP

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Low density lipoprotein increased 610.51 30.24 122 3323 7963 90617039
Myalgia 308.12 30.24 144 3301 174981 90450021
Injection site rash 209.08 30.24 64 3381 24109 90600893
Injection site reaction 162.19 30.24 76 3369 92004 90532998
Injection site erythema 113.45 30.24 61 3384 98441 90526561
Injection site pruritus 93.30 30.24 44 3401 53790 90571212
Injection site pain 88.45 30.24 64 3381 173635 90451367
Blood triglycerides increased 72.28 30.24 25 3420 13736 90611266
Arthralgia 70.39 30.24 114 3331 778408 89846594
Product storage error 66.39 30.24 26 3419 20215 90604787
Peripheral arterial occlusive disease 60.95 30.24 17 3428 4604 90620398
Pain in extremity 46.09 30.24 70 3375 450459 90174543
Immobilisation syndrome 40.81 30.24 8 3437 465 90624537
Apolipoprotein B increased 39.22 30.24 5 3440 14 90624988
Low density lipoprotein abnormal 37.33 30.24 7 3438 321 90624681
Therapy non-responder 37.08 30.24 35 3410 136669 90488333
Rash 34.54 30.24 86 3359 796014 89828988
Fear of death 33.48 30.24 8 3437 1179 90623823
Low density lipoprotein decreased 32.13 30.24 6 3439 269 90624733

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Low density lipoprotein increased 380.71 32.56 85 2793 5270 42613187
Myalgia 302.81 32.56 141 2737 95939 42522518
Leriche syndrome 98.80 32.56 15 2863 98 42618359
Arthralgia 93.26 32.56 90 2788 205148 42413309
Lipoprotein (a) increased 87.72 32.56 16 2862 348 42618109
Spleen ischaemia 66.59 32.56 10 2868 60 42618397
Ischaemic nephropathy 63.23 32.56 10 2868 88 42618369
Blood creatine phosphokinase increased 61.23 32.56 39 2839 48299 42570158
Ulnar nerve injury 61.12 32.56 10 2868 111 42618346
Blood triglycerides increased 58.05 32.56 26 2852 15870 42602587
Peripheral artery bypass 58.01 32.56 9 2869 69 42618388
Myopathy 55.06 32.56 24 2854 13737 42604720
Injection site pain 50.32 32.56 37 2841 57761 42560696
Injection site reaction 48.89 32.56 23 2855 15698 42602759
Low density lipoprotein decreased 47.09 32.56 12 2866 1292 42617165
Drug intolerance 45.51 32.56 40 2838 80384 42538073
Peripheral arterial occlusive disease 44.81 32.56 17 2861 6821 42611636
Low density lipoprotein abnormal 37.35 32.56 8 2870 403 42618054
Low density lipoprotein 36.90 32.56 5 2873 12 42618445
Muscle discomfort 36.02 32.56 7 2871 216 42618241
Myocardial infarction 32.69 32.56 41 2837 123968 42494489

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Low density lipoprotein increased 385.22 27.14 86 3693 10580 110574940
Myalgia 372.62 27.14 171 3608 222210 110363310
Injection site rash 145.51 27.14 47 3732 23372 110562148
Leriche syndrome 103.98 27.14 15 3764 143 110585377
Injection site pain 81.53 27.14 59 3720 177863 110407657
Injection site pruritus 80.86 27.14 38 3741 51220 110534300
Arthralgia 77.92 27.14 113 3666 779519 109806001
Injection site reaction 76.80 27.14 44 3735 89026 110496494
Spleen ischaemia 73.40 27.14 10 3769 60 110585460
Injection site erythema 69.31 27.14 42 3737 94134 110491386
Ischaemic nephropathy 68.88 27.14 10 3769 100 110585420
Blood triglycerides increased 68.33 27.14 27 3752 23899 110561621
Peripheral artery bypass 60.19 27.14 9 3770 112 110585408
Peripheral arterial occlusive disease 59.13 27.14 19 3760 9261 110576259
Ulnar nerve injury 58.99 27.14 10 3769 286 110585234
Acute myocardial infarction 58.15 27.14 36 3743 83741 110501779
Lipoprotein (a) increased 52.36 27.14 8 3771 116 110585404
Blood creatine phosphokinase increased 47.18 27.14 30 3749 73047 110512473
Myocardial infarction 46.47 27.14 44 3735 192039 110393481
Glycosylated haemoglobin increased 45.06 27.14 20 3759 23599 110561921
Low density lipoprotein decreased 38.05 27.14 9 3770 1413 110584107
High density lipoprotein increased 37.76 27.14 9 3770 1460 110584060
Immobilisation syndrome 36.74 27.14 8 3771 868 110584652
Hepatic fibrosis 33.58 27.14 12 3767 8054 110577466
Vascular stent stenosis 32.31 27.14 8 3771 1521 110583999
Apolipoprotein B increased 31.85 27.14 4 3775 11 110585509
Fear of death 31.62 27.14 8 3771 1659 110583861
Lipoprotein increased 30.32 27.14 4 3775 18 110585502
Muscle spasms 28.57 27.14 41 3738 278116 110307404
Peripheral artery occlusion 27.22 27.14 8 3771 2897 110582623

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC C10AX16 CARDIOVASCULAR SYSTEM
LIPID MODIFYING AGENTS
LIPID MODIFYING AGENTS, PLAIN
Other lipid modifying agents
CHEBI has role CHEBI:35554 cardiovascular drug
CHEBI has role CHEBI:35821 anticholesteremic drug
CHEBI has role CHEBI:145947 antiatherosclerotic agent
CHEBI has role CHEBI:231911 renoprotective agent

Related Drugs by ATC class:

C10AX Other lipid modifying agents 15 drugs
alipogene tiparvovecalirocumabbempedoic aciddextrothyroxineevinacumabevolocumabezetimibelerodalcibep-ligalomitapidemeglutolmipomersenpolicosanol show all 15 →

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

DiseaseRelationSNOMED_IDDOID
Atherosclerotic cardiovascular disease indication 72092001
Familial hypercholesterolemia - heterozygous indication 238079002




🐶 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 strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 8809292 May 10, 2027 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF ADULTS WITH HYPERCHOLESTEROLEMIA, INCLUDING HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH), BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 8809292 May 10, 2027 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF PEDIATRIC PATIENTS AGED 12 YEARS AND OLDER WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH) BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 8809292 May 10, 2027 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF PEDIATRIC PATIENTS AGED 12 YEARS AND OLDER WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HOFH), BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 8222222 Dec. 29, 2027 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF ADULTS WITH HYPERCHOLESTEROLEMIA, INCLUDING HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH), BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 8222222 Dec. 29, 2027 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF PEDIATRIC PATIENTS AGED 12 YEARS AND OLDER WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH) BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 8222222 Dec. 29, 2027 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF PEDIATRIC PATIENTS AGED 12 YEARS AND OLDER WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HOFH), BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 10131907 Aug. 24, 2028 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF ADULTS WITH HYPERCHOLESTEROLEMIA, INCLUDING HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH), BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 10131907 Aug. 24, 2028 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF PEDIATRIC PATIENTS AGED 12 YEARS AND OLDER WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH) BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 10131907 Aug. 24, 2028 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF PEDIATRIC PATIENTS AGED 12 YEARS AND OLDER WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HOFH), BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 8828956 Dec. 4, 2028 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF ADULTS WITH HYPERCHOLESTEROLEMIA, INCLUDING HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH), BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 8828956 Dec. 4, 2028 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF PEDIATRIC PATIENTS AGED 12 YEARS AND OLDER WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH) BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 8828956 Dec. 4, 2028 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF PEDIATRIC PATIENTS AGED 12 YEARS AND OLDER WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HOFH), BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 9370582 Dec. 4, 2028 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF ADULTS WITH HYPERCHOLESTEROLEMIA, INCLUDING HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH), BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 9370582 Dec. 4, 2028 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF PEDIATRIC PATIENTS AGED 12 YEARS AND OLDER WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH) BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 9370582 Dec. 4, 2028 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF PEDIATRIC PATIENTS AGED 12 YEARS AND OLDER WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HOFH), BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 8106022 Dec. 12, 2029 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF ADULTS WITH HYPERCHOLESTEROLEMIA, INCLUDING HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH), BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 8106022 Dec. 12, 2029 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF PEDIATRIC PATIENTS AGED 12 YEARS AND OLDER WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH) BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 8106022 Dec. 12, 2029 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF PEDIATRIC PATIENTS AGED 12 YEARS AND OLDER WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HOFH), BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 10125369 Aug. 18, 2034 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF ADULTS WITH HYPERCHOLESTEROLEMIA, INCLUDING HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH), BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 10125369 Aug. 18, 2034 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF PEDIATRIC PATIENTS AGED 12 YEARS AND OLDER WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH) BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 10125369 Aug. 18, 2034 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF PEDIATRIC PATIENTS AGED 12 YEARS AND OLDER WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HOFH), BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 10851377 Aug. 25, 2036 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF ADULTS WITH HYPERCHOLESTEROLEMIA, INCLUDING HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH), BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 10851377 Aug. 25, 2036 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF PEDIATRIC PATIENTS AGED 12 YEARS AND OLDER WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH) BY INHIBITING EXPRESSION OF THE PCSK9 GENE
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS 10851377 Aug. 25, 2036 AS AN ADJUNCT TO DIET AND EXERCISE FOR THE TREATMENT OF PEDIATRIC PATIENTS AGED 12 YEARS AND OLDER WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HOFH), BY INHIBITING EXPRESSION OF THE PCSK9 GENE

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS Dec. 22, 2026 NEW CHEMICAL ENTITY
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS Feb. 12, 2029 INDICATED AS AN ADJUNCT TO DIET AND EXERCISE TO REDUCE LDL-C IN PEDIATRIC PATIENTS 12 YEARS AND OLDER WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA
EQ 284MG BASE/1.5ML (EQ 189MG BASE/ML) LEQVIO NOVARTIS N214012 Dec. 22, 2021 RX SOLUTION SUBCUTANEOUS Feb. 12, 2029 NEW PATIENT POPULATION

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Asialoglycoprotein receptor 1 Membrane receptor BINDING AGENT UNKNOWN DRUG LABEL
Asialoglycoprotein receptor 2 Membrane receptor BINDING AGENT UNKNOWN DRUG LABEL
Proprotein convertase subtilisin/kexin type 9 Enzyme ANTISENSE INHIBITOR IC50 11.54 DRUG LABEL DRUG LABEL

External reference:

IDSource
CHEBI:176399 CHEBI
CHEMBL3990033 ChEMBL_ID
C585830 MESH_SUPPLEMENTAL_RECORD_UI
13624 IUPHAR_LIGAND_ID
DB14901 DRUGBANK_ID
1306560009 SNOMEDCT_US
39492511000001108 SNOMEDCT_US
4041078 VANDF
C4307388 UMLSCUI
D11931 KEGG_DRUG
CHEMBL5095052 ChEMBL_ID
10268 INN_ID
345011 MMSL
d09728 MMSL
018725 NDDF
UOW2C71PG5 UNII
2588243 RXNORM

Pharmaceutical products:

None