From: Recent advances in the discovery and development of drugs targeting the kallikrein-kinin system
Drug candidate | Class | Intended indication | Current trial phase | Year of latest publication | Refs. |
---|---|---|---|---|---|
C1 esterase inhibitor | |||||
 BMN 331 | AAV5-based gene transfer | Hereditary angioedema (prophylaxis) | 1/2 | Study ongoing | [120] |
 Human C1 esterase inhibitor | Protein replacement therapy | ACEi-induced angioedema | 3 | 2022 | [116] |
Acute antibody-mediated rejection after kidney transplant | 3 | 2020 | [115] | ||
Delayed graft function after kidney transplant* | 1/2 | 2020 | [114] | ||
Neuromyelitis optica | 1 | 2014 | [162] | ||
 Conestat alfa | Protein replacement therapy | Stroke prevention after transcatheter aortic valve transplantation | 2 | Study ongoing | [119] |
COVID-19* | 2 | 2021 | Â | ||
Amoreliate adverse events of intravenous immunoglobulin therapy | 4 | 2021 | [118] | ||
Coagulation factor XII | |||||
 Garadacimab/CSL312 | Monoclonal antibody (fully human) | COVID-19 | 2 | 2023 | [28] |
Idiopathic pulmonary fibrosis | 2 | (2024) | [29] | ||
Catheter-associated blood clot formation in subjects with cancer who receive chemotherapy through a PICC line* | 1/2 | (2020) | [30] | ||
 Ixodes ricinus-contact phase inhibitor (Ir-CPI) | Inhibitor, protein | Thromboprophylaxis during cardiopulmonary bypass surgery | 1 | (2023) | |
Plasma (P) and tissue (T) kallikrein | |||||
 ADX-324 (P) | siRNA | Hereditary angioedema (prophylaxis) | 1 | (2023) | [70] |
 ATN-249 (P) | Small molecule inhibitor | Hereditary angioedema (prophylaxis) | 1 | 2017 | [63] |
 Avoralstat/BCX4161 (P) | Small molecule inhibitor | Hereditary angioedema (prophylaxis) | 3 | 2018 | [59] |
 Donidalorsen/IONIS-PKK-LRX (P) | Antisense oligonucleotide | Hereditary angioedema (prophylaxis) | 3 | 2022 | |
COVID-19 | 2 | (2020) | [163] | ||
 IONIS-PKKRX (P) | Antisense oligonucleotide | Hereditary angioedema (prophylaxis) | 2 | 2020 | [66] |
Chronic migraine | 2 | 2020 | [67] | ||
 KVD001 (P) | Small molecule inhibitor | Diabetic macular edema | 2 | 2019 | [72] |
 KVD824 (P) | Small molecule inhibitor | Hereditary angioedema (prophylaxis)* | 2 | (2022) | [62] |
 Lanadelumab/DX-2930 (P) | Monoclonal antibody (fully human) | Dialysis-induced hypotension | 2 | Study ongoing | [76] |
FXII-associated cold autoinflammatory syndrome | 2 | Study ongoing | [78] | ||
Lung injury | 1 | Study ongoing | [77] | ||
 NTLA-2002 (P) | CRISPR/CAS 9 gene editing | Hereditary angioedema (prophylaxis) | 1/2 | Study ongoing | |
 RZ402 (P) | Small molecule inhibitor | Diabetic macular edema | 2 | Study ongoing | [75] |
 Sebetralstat/KVD900 (P) | Small molecule inhibitor | Hereditary angioedema (on-demand) | 3 | 2023 | |
 STAR-0215 (P) | Monoclonal antibody (humanized) | Hereditary angioedema (prophylaxis) | 2 | Study ongoing | - |
 THR-149 (P) | Peptide inhibitor | Diabetic macular edema | 2 | Study ongoing | [73] |
 MDCO-2010 (P, T) | Small molecule inhibitor | Reduction of blood loss during coronary artery bypass graft surgery* | 2 | 2014 | |
 Aprotinin (P, T) | Inhibitor, protein | COVID-19 | 3 | 2022 | |
 DM199 (recombinant tissue kallikrein) (T) | Enzyme replacement therapy | Acute ischemic stroke | 2/3 | (2022) | |
Kidney disease | 2 | (2022) | [106] | ||
Diabetes mellitus type 2 | 2 | (2014) | [105] | ||
 Porcine pancreatic pig tissue kallikrein (T) | Enzyme replacement therapy | Restenosis after stenting of symptomatic middle cerebral artery (MCA) atherosclerotic stenosis | 2 | 2016 | [102] |
Bradykinin B2 receptor | |||||
 Anatibant/LF 16-0687 | Small molecule antagonist | Traumatic brain injury* | 2 | 2009 | [129] |
 Deltibant/CP-1027/Bradycor | Peptide antagonist | Traumatic brain injury | 2 | 1999 | [128] |
 Deucrictibant/PHA-022121 | Small molecule antagonist | Hereditary angioedema (on-demand) | 2 | 2022 | [127] |
 Fasitibant/MEN16132 | Small molecule antagonist | Knee osteoarthritis* | 2 | 2015 | [130] |
 Icatibant/HOE 140 | Peptide antagonist | Dialysis-induced hypotension | 2 | 2023 | |
ACEi-induced upper airway angioedema | 3 | 2017 | |||
 Labradimil/RMP-7 | Peptide agonist | Primary brain tumors* | 2 | 2006 | |
Bradykinin B1 receptor | |||||
 BAY 2395840 | Antagonist | Diabetic neuropathic pain* | 2 | (2023) | |
 BI 1026706 | Small molecule antagonist | Diabetic macular edema | 2 | 2020 | [144] |
 Safotibant/LF22-0542 | Small molecule antagonist | Diabetic macular edema* | 2 | 2012 | [145] |