Drugs in trials for the treatment of AI
| Disease context . | Drug . | Type of drug . | Target . | Beneficial effects on AI . | Stage . |
|---|---|---|---|---|---|
| CKD | P2D7KK | Antibody | IL-1β | ↓ inflammation ↑ renal function ↓ anemia | Preclinical183 |
| KY1070 | Antibody | BMP6 | ↓ hepcidin ↑ erythroid response | Preclinical184 | |
| Ziltivekimab | Antibody | IL-6 | ↓ inflammation ↓ ESA requirements ↓ iron restriction | Clinical (phase 1/2)185 | |
| PRS-080#22 | Anticalin protein | Hepcidin | ↓ hepcidin ↑ iron mobilization | Clinical (phase 1)186 | |
| LY2928057 | Antibody | FPN/hepcidin binding | ↑ serum iron ↓ Hb decline after discontinuation of standard treatment | Clinical (phase 1/2)187 | |
| Vadadustat | Small molecule | HIF-PH | Noninferior to ESAs in the maintenance of Hb concentrations | Clinical (phase 3)188 | |
| Roxadustat | Small molecule | HIF-PH | Noninferior to ESAs in patients undergoing dialysis | Clinical (phase 3)189 | |
| Daprodustat | Small molecule | HIF-PH | Noninferior to ESAs for increase in Hb | Clinical (phase 3)190 | |
| CD | Infliximab | Antibody | TNFα | ↓ hepcidin ↑ serum iron ↑ Hb | FDA/EMA approved191-193 |
| RA | Tocilizumab | Antibody | IL-6 receptor | ↓ inflammation ↓ hepcidin ↑ Hb, RBC counts | FDA/EMA approved194,195 |
| Advanced cancer | Lactoferrin | Iron-binding protein | Similar efficacy for oral lactoferrin and for IV iron, combined with rHuEPO | Clinical (phase 1)196 | |
| ALD518 | Antibody | IL-6 | ↑ Hb | Clinical (phase 2)197 | |
| Endotoxemia | Lexaptepid | Small molecule | Hepcidin | Transient ↑ serum iron | Clinical (phase 1)198 |
| Disease context . | Drug . | Type of drug . | Target . | Beneficial effects on AI . | Stage . |
|---|---|---|---|---|---|
| CKD | P2D7KK | Antibody | IL-1β | ↓ inflammation ↑ renal function ↓ anemia | Preclinical183 |
| KY1070 | Antibody | BMP6 | ↓ hepcidin ↑ erythroid response | Preclinical184 | |
| Ziltivekimab | Antibody | IL-6 | ↓ inflammation ↓ ESA requirements ↓ iron restriction | Clinical (phase 1/2)185 | |
| PRS-080#22 | Anticalin protein | Hepcidin | ↓ hepcidin ↑ iron mobilization | Clinical (phase 1)186 | |
| LY2928057 | Antibody | FPN/hepcidin binding | ↑ serum iron ↓ Hb decline after discontinuation of standard treatment | Clinical (phase 1/2)187 | |
| Vadadustat | Small molecule | HIF-PH | Noninferior to ESAs in the maintenance of Hb concentrations | Clinical (phase 3)188 | |
| Roxadustat | Small molecule | HIF-PH | Noninferior to ESAs in patients undergoing dialysis | Clinical (phase 3)189 | |
| Daprodustat | Small molecule | HIF-PH | Noninferior to ESAs for increase in Hb | Clinical (phase 3)190 | |
| CD | Infliximab | Antibody | TNFα | ↓ hepcidin ↑ serum iron ↑ Hb | FDA/EMA approved191-193 |
| RA | Tocilizumab | Antibody | IL-6 receptor | ↓ inflammation ↓ hepcidin ↑ Hb, RBC counts | FDA/EMA approved194,195 |
| Advanced cancer | Lactoferrin | Iron-binding protein | Similar efficacy for oral lactoferrin and for IV iron, combined with rHuEPO | Clinical (phase 1)196 | |
| ALD518 | Antibody | IL-6 | ↑ Hb | Clinical (phase 2)197 | |
| Endotoxemia | Lexaptepid | Small molecule | Hepcidin | Transient ↑ serum iron | Clinical (phase 1)198 |
Despite the efficacy of hypoxia-inducible factor prolyl hydroxylases inhibitors (HIF-PHIs) to ameliorate anemia in the context of CKD, these drugs have not been licensed for clinical use in the United States (FDA), whereas they were approved by the European authorities (EMA). The FDA justified its decision by the fact that HIF-PHIs activate numerous HIF target genes in different organs. Specifically, the higher frequency of thromboembolic events, acceleration of diabetic retinopathy, or progression of malignancy in some patients treated with HIF-PHIs raised concerns.199,200
CD, Crohn disease; EMA, European Medicines Agency; FDA, Food and Drug Administration; HIF-PH, hypoxia-inducible factor prolyl hydroxylase; rHuEPO, recombinant human erythropoietin.