Table 1. Targeting the intrinsic pathway of coagulation and the kallikrein-kinin system. The intrinsic pathway and the kallikrein-kinin system are both activated by factor XIIa. The table below is a selected list of compounds against components of the pathways that are in clinical development or on the market.

Source: BioCentury Archives

Target

Company

Compound

Status

Indication

Factor XI

Isis Pharmaceuticals Inc. (NASDAQ:ISIS)

ISIS-FXIRx
(antisense oligonucleotide)

Phase II

Block coagulation

Factor IXa

Regado Biosciences Inc. (NASDAQ:RGDO)

Pegnivacogin
(aptamer)

Phase II

Block coagulation

Factor Xa

Alchemia Ltd. (ASX:ACL); Dr. Reddy's Laboratories Ltd. (NYSE:RDY)

Fondared fondaparinux
(small molecule)

Marketed

Deep vein thrombosis (DVT)

 

 

Bayer AG (Xetra:BAYN); Almirall S.A. (Madrid:ALM); Johnson & Johnson (NYSE:JNJ)

Xarelto rivaroxaban
(small molecule)

Marketed

DVT; venous thromboembolism (VTE); pulmonary embolism (PE); stroke

Registration

Acute coronary syndrome (ACS)

 

 

Bristol-Myers Squibb Co. (NYSE:BMY); Pfizer Inc. (NYSE:PFE)

Eliquis apixaban
(small molecule)

Marketed

VTE; stroke

Registration

DVT

 

 

Daiichi Sankyo Co. Ltd. (Tokyo:4568)

Lixiana edoxaban
(small molecule)

Marketed

VTE

Registration

Atrial fibrillation (AF); stroke; DVT; PE; VTE

 

 

GlaxoSmithKline plc (LSE:GSK; NYSE:GSK)

Arixtra fondaparinux
(small molecule)

Marketed

DVT

Approved

ACS; PE; VTE

 

Sanofi (Euronext:SAN; NYSE:SNY)

Idraparinux
(polysaccharide)

Phase III

DVT; thrombosis with AF

 

 

Portola Pharmaceuticals Inc. (NASDAQ:PTLA)

Betrixaban
(small molecule)

Phase III

VTE

Phase II

Stroke

 

TeaRx LLC; Roche (SIX:ROG; OTCQX:RHHBY)

TeaRxaban
(unknown)

Phase II

Thrombosis; VTE

 

Green Cross Corp. (KSE:006280)

GCC4401C
(small molecule)

Phase I

VTE; stroke

Thrombin (factor IIa; F2)

Asahi Kasei Pharma Corp.

Recomodulin
(peptide)

Marketed

Block coagulation

 

Bayer

Refludan
(biologic)

Marketed

Thrombosis; thrombocytopenia

 

 

 

Boehringer Ingelheim GmbH

Pradax dabigatran
(small molecule)

Marketed

VTE

Registration

Thrombosis

Phase II

Coronary artery disease (CAD)

 

Eagle Pharmaceuticals Inc. (NASDAQ:EGRX); The Medicines Co. (NASDAQ:MDCO)

Ready-to-use argatroban
(small molecule)

Marketed

Thrombosis

 

The Medicines Co.; AstraZeneca plc (LSE:AZN; NYSE:AZN); Grupo Ferrer Internacional S.A.

Angiomax bivalirudin
(small molecule)

Marketed

ACS; angina angioplasty; percutaneous coronary intervention (PCI); thrombosis; thrombocytopenia

 

Mitsubishi Tanabe Pharma Corp. (Tokyo:4508); GSK

Arganova argatroban
(small molecule)

Marketed

Blood clots; thrombosis; thrombocytopenia

 

AstraZeneca

AZD0837
(small molecule)

Phase II

Thrombosis

 

Archemix Corp.; Arca biopharma Inc. (NASDAQ:ABIO)

ARC2172
(aptamer)

Phase I

Block coagulation

 

Diakron Pharmaceutical Inc.; Orchid Chemicals & Pharmaceuticals Ltd. (BSE:524372; NSE:ORCHIDCHEM)

DP-4088
(small molecule)

Phase I

Thrombosis

Factor Xa; F2

Abbott Laboratories (NYSE:ABT)

Clivarin reviparin
(low-molecular weight heparin (LMWH))

Marketed

DVT

 

Leo Pharma A/S; Celgene Corp. (NASDAQ:CELG)

Innohep tinzaparin
(LMWH)

Marketed

DVT

 

Momenta Pharmaceuticals Inc. (NASDAQ:MNTA); Novartis AG (NYSE:NVS; SIX:NOVN)

M-enoxaparin
(LMWH)

Marketed

DVT; ACS

 

Pfizer; Eisai Co. Ltd. (Tokyo:4523)

Fragmin dalteparin
(LMWH)

Marketed

CAD; DVT; ischemia/reperfusion injury; VTE

 

Sanofi

Klexane R enoxaparin
(LMWH)

Marketed

Unstable angina; non-ST segment elevation myocardial infarction (NSTEMI); DVT; myocardial infarction (MI); VTE

 

Amphastar Pharmaceuticals Inc.; Actavis plc (NYSE:ACT)

Enoxaparin
(LMWH)

Approved

DVT

 

Merck & Co. Inc. (NYSE:MRK); Endotis Pharma

EP217609
(unknown)

Phase II

Prevent coagulation during extracorporeal circulation (ECC)

 

Momenta Pharmaceuticals

M118
(LMWH)

Phase II

ACS

Fibrin

 

 

Genentech Inc. unit of Roche; Boehringer Ingelheim

Metalyse tenecteplase
(biologic: enzyme)

Marketed

MI

Phase III

Catheter clearance

Phase II

Stroke

 

Fibrex Medical Inc.; Ikaria Inc.

FX06MRI
(peptide)

Phase II

Ischemia/reperfusion injury

 

Grifols S.A. (Madrid:GRF; NASDAQ:GRFS)

Plasmin
(biologic: enzyme)

Phase II

Peripheral vascular disease

 

BioCryst Pharmaceuticals Inc. (NASDAQ:BCRX)

BCX4161
(small molecule)

Phase II

Hereditary angioedema (HAE)

Kallikrein

Dyax Corp. (NASDAQ:DYAX); Lee's Pharmaceutical Holdings Ltd. (HKSE:0950); Sigma-Tau Group; taiba Pharma LLC

Kalbitor ecallantide
(peptide)

Marketed

Angioedema; HAE

 

Dyax

DX-2930
(antibody)

Phase I

HAE

Bradykinin B2 receptor (BDKRB2; B2R)

Sanofi; Shire plc (LSE:SHP; NASDAQ:SHPG)

Firazyr icatibant
(small molecule)

Marketed

Angioedema; HAE