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Table 2 Drug candidates in clinical development with targets in the kallikrein-kinin system

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

 

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)

[31,32,33]

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

[66, 68, 69]

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

[64, 65]

 RZ402 (P)

Small molecule inhibitor

Diabetic macular edema

2

Study ongoing

[75]

 Sebetralstat/KVD900 (P)

Small molecule inhibitor

Hereditary angioedema (on-demand)

3

2023

[60, 61]

 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

[97, 98]

 Aprotinin (P, T)

Inhibitor, protein

COVID-19

3

2022

[93, 94]

 DM199 (recombinant tissue kallikrein) (T)

Enzyme replacement therapy

Acute ischemic stroke

2/3

(2022)

[103, 104]

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

[125, 126]

ACEi-induced upper airway angioedema

3

2017

[123, 124]

 Labradimil/RMP-7

Peptide agonist

Primary brain tumors*

2

2006

[134, 135]

Bradykinin B1 receptor

 BAY 2395840

Antagonist

Diabetic neuropathic pain*

2

(2023)

[146, 147]

 BI 1026706

Small molecule antagonist

Diabetic macular edema

2

2020

[144]

 Safotibant/LF22-0542

Small molecule antagonist

Diabetic macular edema*

2

2012

[145]

  1. Year of latest publication: Years are those of the most recent publications found in peer-reviewed journals
  2. Years in parentheses indicate press releases, poster presentations at conferences or announcements on clinicaltrials.gov
  3. Study ongoing means that the study is currently ongoing and there are no publications from previous studies
  4. *Indicates that development of the drug candidate for this indication was discontinued during clinical trials
  5. (P) and (T) indicate whether plasma (P) or tissue (T) kallikrein is the target of the active pharmaceutical ingredient
  6. AAV = adeno-associated virus; ACEi = angiotensin-converting enzyme inhibitor; COVID-19 = coronavirus disease 2019; CRISPR/Cas9 = clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9; FXII = coagulation factor XII; PICC = Peripherally inserted central catheter; siRNA = small interfering ribonucleic acid
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Journal of Translational Medicine

ISSN: 1479-5876

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