TABLE 3.
Transforming growth factor-beta (TGF-β) pathway inhibitors (approved, currently in clinical trials, or preclinical) potentially relevant to COVID-19 prevention or treatment.
| Drug | Manufacturer | Route | Mechanism | Status diseases | Clinical trials | Clinical trial stage/Findings (as of 8/2022) |
| GSK3008348 | Glaxo | Inhaled | ανβ6 integrin inhibitor | Investigational lung fibrosis |
NCT02612051 NCT03069989 NCT02612051 |
Phase I Ongoing or completed/Unpublished |
| PLN-74809 | Pliant Therapeutics |
Oral | Small molecule ανβ6/ανβ1 integrin inhibitor |
Investigational lung fibrosis cholangitis |
NCT04072315 NCT04396756 NCT04480840 |
Phase IIa Ongoing or completed/Unpublished |
| MORF-720 | Morphic (AbbVie) |
Oral | Small molecule ανβ6, 4β7 integrin inhibitors |
Pre-clinical fibrosis cancer |
NA | NA |
| LY2157299 (Galunisertib) |
Eli Lilly | Oral | Small molecule, TGFβRIi | Investigational cancer |
Of 25 trials: NCT02304419 NCT02008318 |
Phase 1–3 Well-tolerated, benefit seen in phase 2 studies |
|
LY573636 (Tasisulam) |
Eli Lilly | IV | Small molecule, TGFβRIi; long half-life | Investigational cancer |
Of 13 studies: NCT00992225 |
Phase 2 Hepatic and marrow toxicity |
| LY3200882 | Eli Lilly | Oral | Small molecule, TGFβRIi | Investigational cancer |
Of 4 trials: NCT04031872 NCT02937272 |
Phase 1–2 Well-tolerated |
| Vactosertib (TEW7197) |
Bristol Myers Squibb (Forbius) | Oral | Small molecule, TGFβRIi | Investigational cancer |
Of 17 trials: NCT03074006 NCT04515979 |
Phase 2 Ongoing or completed/Unpublished |
| SRI-35241 | Southern Research | IV | Small molecule Inhibits activation of latent TGFβ |
Preclinical fibrosis |
Preclinical | Preclinical |
| Epigallocatechin Gallate (ECGC) |
Multiple producers |
Oral | Green tree extract Catechin Kinase inhibitor |
Investigational lung fibrosis many diseases |
Of 104 trials: NCT03928847 NCT03928847 |
Marketed as over-the-counter supplement (FDA approval not required) |
| AVID200 | Bristol Myers Squibb (Forbius) |
IV | TGFβ 1/3 trap | Investigational cancer skin fibrosis myelofibrosis |
NCT03831438 NCT03834662 NCT03895112 |
Phase 2 Well-tolerated, biologic effects demonstrated in vivo |
| Luspatercept | Acceleron (Merck) |
SQ | TGFβ trap (ACtRIIb) | FDA-approved myelofibrosis thalassemia |
Of 25 trials: NCT02604433 NCT04717414 |
Marketed after phase 3 trials Improves hemoglobin levels Other indications being tested in clinical trials |
| Sotatercept (ACE-001) |
Acceleron (Merck) |
SQ | TGFβ trap (ACtRIIa) | Investigational pulmonary hypertension |
Of 21 trials: NCT03496207 NCT04896008 |
Phase 2 |
| Bintrafusp-α (M7824) |
EMD Serrano (Merck-GSK) |
IV | Bifunctional Ab: TGFβ-trap, aPDL1 | Investigational cancer |
Of 46 trials: NCT02517398 NCT04727541 |
Phase 1–2; ongoing or completed Tolerable (rash, pruritis) |
| Dalutrafusp-α (GS-1423) |
Gilead | IV | Bifunctional Ab: aCD73, TGFβ-Trap |
Investigational cancer |
NCT03954704 | Phase 1, terminated |
| Trabedersen AP12009 OT-101 |
Autotelic (Isarna) |
IV topical |
Antisense RNA to TGFβ2 |
Investigational cancer COVID-19 myopia |
NCT00844064 NCT00431561 NCT00761280 NCT04801017 |
Phase 2–3 Ongoing or completed/Unpublished |
| ISTH0036 | Isarna Therapeutics | Eye | Antisense RNA to TGFβ1 |
Investigational glaucoma AMD |
NCT02406833 | Phase 2, Ongoing |
| TRK-250 | Toray Industries | Inhaled | Antisense RNA to TGFβ1 |
Investigational Lung fibrosis |
NCT03727802 | Phase 1, Ongoing |
| XOMA089 | Novartis | IV/SQ | TGFβ 1-3 Ab (all isoforms) |
Preclinical | NA | NA |
| LY2382770 | Eli Lilly | SQ | TGFβ1 Ab | Investigational kidney disease |
NCT01113801 | Phase 2, completed No clinical benefit to date Well-tolerated |
| Fresolimumab (GC1008) |
Sanofi | IV | TGFβ 1-3 Ab (to all isoforms) |
Investigational cancer fibrosis |
Of 12 trials: NCT00125385 NCT01665391 |
Phase 2; completed No clinical benefit to date Skin toxicity |
| SRK-181 | Gilead (Scholar-Rock) | IV | Latent-TGFβ1 Ab | Investigational cancer |
NCT04291079 | Phase 1, Ongoing |
| NA | Merck (Tilos) | IV | Anti-LAP integrin Ab | Pre-clinical cancer |
NA | NA |
| BG00011 (STX100) |
Biogen | SQ | anti-αvβ6 integrin Ab | Investigational Lung fibrosis |
NCT01371305 | Phase 2, unpublished Trials stopped early 2017 |
| VTX-001 | Venn Therapeutics | IV/SQ | anti-αvβ6 integrin Ab | Pre-clinical fibrosis |
None to date | NA |
Some pre-clinical agents and other agents with halted development are not shown. Only one drug is FDA-approved (luspatercept), and only one drug is currently in COVID-19 clinical trials (trabedersen). Ab, antibody; ACtRIIa, activin receptor IIa; ACtRIIb, activin receptor IIb; AMD, adult macular degeneration; aPDL1, anti-programmed death ligand 1; IV, intravenous; LAP, latency activating peptide; NA, not applicable; SQ, subcutaneous; TGF-β, transforming growth factor beta; TGFβIR, TGF-β receptor I, also known as ALK5; TGFβR2 trap, Fc-based compound containing copies of TGF-β receptor II; TGFβRIi, TGF-β receptor I inhibitor.