Potential enhancers of erythropoiesis in ongoing or imminent clinical trials
| Drug name and drug class . | Molecular target . | Secondary effect . | Potential applications in thalassemias . | Route and frequency of administration . | Clinical trial stage . | Observed clinical effects to date . | Company . | Ref . |
|---|---|---|---|---|---|---|---|---|
| Sotatercept (ACE-011) activin receptor IIa | Trap for TGF-β ligands | Decreased GDF11 signaling; increased erythropoiesis effectiveness | Improved Hb and QOL in non-TDT; reduced transfusion in TDT | Subcutaneous, 3 weekly | Phase 2a for thalassemia | Dose-dependent Hb increase 1-2 g/dL in non-TDT; decreased transfusion in some TDT | Celgene, Acceleron | See text |
| Luspatercept (ACE-536) activin receptor IIb | As above | As above | As above | Subcutaneous, 3 weekly | Phase 3 for thalassemia | Improved anemia in non-TDT as above; improved QOL; improved 6-min walk; decreased transfusion in some TDT | Celgene, Acceleron | See text |
| PTG-300 hepcidin derivative | Ferroportin | Hepcidin mimetic increases effectiveness of erythropoiesis | Improved erythropoiesis | Subcutaneous | Phase 1: no serious adverse events expected; hypoferremia observed | Prolonged plasma half-life and serum iron decrease | Protagonist Therapeutics | Presented EHA 2018 (abstract S843) |
| LJPC-401 synthetic hepcidin formulation | Ferroportin | Hepcidin mimetic synthetic hepcidin | Secondary iron overload distribution | Subcutaneous | Phase 1: no toxicity reported, healthy volunteers | Expected hypoferremia observed | La Jolla Pharmaceutical Company | Presented EHA 2018 (abstract S894) |
| Tmprss6-siRNA | Tmprss6 | As above | Improved erythropoiesis | Subcutaneous | Validated in preclinical studies | NYR | Alnylam Pharmaceuticals | Animal model ASH (2013) |
| Tmprss6-ASO | Tmprss6 | Stimulates hepcidin production by suppressing Tmprss6 | Improved erythropoiesis | Subcutaneous | Phase 1 ongoing | NYR | Ionis Pharmaceuticals | Ionis Pharma press release; in pipeline |
| SLN124 Tmprss6-siRNA | Tmprss6 | As above | Improved erythropoiesis; iron overload | Subcutaneous | Phase 1 planned for late 2019 | NYR | Silence Therapeutics | Animal data presented EHA (2018) (abstract S893) |
| VIT-2763 ferroportin inhibitor | Ferroportin | Ferroportin inhibitors | Prevent iron overload; improved erythropoiesis decrease | Oral | Phase 1 planned for late 2018 | NYR | Vifor Pharma | Vifor press release (2018) |
| MHs (PR65, PR73, M009, M012) | Ferroportin | Hepcidin mimetic (mini-hepcidin) low MW | As above | Subcutaneous | Preclinically validated in early clinical trials | NYR | University of California, Los Angeles | 36 |
| Drug name and drug class . | Molecular target . | Secondary effect . | Potential applications in thalassemias . | Route and frequency of administration . | Clinical trial stage . | Observed clinical effects to date . | Company . | Ref . |
|---|---|---|---|---|---|---|---|---|
| Sotatercept (ACE-011) activin receptor IIa | Trap for TGF-β ligands | Decreased GDF11 signaling; increased erythropoiesis effectiveness | Improved Hb and QOL in non-TDT; reduced transfusion in TDT | Subcutaneous, 3 weekly | Phase 2a for thalassemia | Dose-dependent Hb increase 1-2 g/dL in non-TDT; decreased transfusion in some TDT | Celgene, Acceleron | See text |
| Luspatercept (ACE-536) activin receptor IIb | As above | As above | As above | Subcutaneous, 3 weekly | Phase 3 for thalassemia | Improved anemia in non-TDT as above; improved QOL; improved 6-min walk; decreased transfusion in some TDT | Celgene, Acceleron | See text |
| PTG-300 hepcidin derivative | Ferroportin | Hepcidin mimetic increases effectiveness of erythropoiesis | Improved erythropoiesis | Subcutaneous | Phase 1: no serious adverse events expected; hypoferremia observed | Prolonged plasma half-life and serum iron decrease | Protagonist Therapeutics | Presented EHA 2018 (abstract S843) |
| LJPC-401 synthetic hepcidin formulation | Ferroportin | Hepcidin mimetic synthetic hepcidin | Secondary iron overload distribution | Subcutaneous | Phase 1: no toxicity reported, healthy volunteers | Expected hypoferremia observed | La Jolla Pharmaceutical Company | Presented EHA 2018 (abstract S894) |
| Tmprss6-siRNA | Tmprss6 | As above | Improved erythropoiesis | Subcutaneous | Validated in preclinical studies | NYR | Alnylam Pharmaceuticals | Animal model ASH (2013) |
| Tmprss6-ASO | Tmprss6 | Stimulates hepcidin production by suppressing Tmprss6 | Improved erythropoiesis | Subcutaneous | Phase 1 ongoing | NYR | Ionis Pharmaceuticals | Ionis Pharma press release; in pipeline |
| SLN124 Tmprss6-siRNA | Tmprss6 | As above | Improved erythropoiesis; iron overload | Subcutaneous | Phase 1 planned for late 2019 | NYR | Silence Therapeutics | Animal data presented EHA (2018) (abstract S893) |
| VIT-2763 ferroportin inhibitor | Ferroportin | Ferroportin inhibitors | Prevent iron overload; improved erythropoiesis decrease | Oral | Phase 1 planned for late 2018 | NYR | Vifor Pharma | Vifor press release (2018) |
| MHs (PR65, PR73, M009, M012) | Ferroportin | Hepcidin mimetic (mini-hepcidin) low MW | As above | Subcutaneous | Preclinically validated in early clinical trials | NYR | University of California, Los Angeles | 36 |
ASH, American Society of Hematology; EHA, European Hematology Association; NYR, not yet reported.