Table 5.
Antifibrotics in clinical development
| Company | Compound | Mechanism of action | Route | Indications | Status of project |
|---|---|---|---|---|---|
| Intermune, Shionogi | Pirfenidone | Unknown, reduces growth factors/cytokines | Oral | IPF, DN, FSGS | Approved in Japan and Europe for IPF, Phase III for IPF in United States, Phase II for DN and FSGS |
| Intermune | ActImmune™ | Recombinant human IFN- | Subcut. | IPF | Failed in Phase III for IPF |
| Actelion Pharmaceuticals | Bosentan (Tracleer™) | Endothelin antagonist | Oral | IPF | Failed in Phase III for IPF |
| Gilead | Ambrisentan (Letiaris) | Endothelin antagonist | Oral | IPF | Phase III |
| Pfizer | Sildenafil (Revatio) | PDE5 inhibitor | Oral | PAH in IPF | Phase III |
| Boehringer Ingelheim | BIBF-1120 (Vargatef ) | VEGFR, FGFR, PDGFR inhibitor | Oral | IPF | Phase III |
| Abbott/Reatta | Bardoxolone methyl | Nrf2 agonist, PDJ2 mimetic | Oral | CKD in DN | Phase III |
| Novartis | Imatinib mesylate (Gleevec) | PDGFR-α/β inhibitor | Oral | IPF, DN | Failed in Phase II for IPF, Phase II for DN |
| Celgene | Thalidomide (Thalomid) | Unknown, reduces collagen production | Oral | IPF, MF | Phase II in IPF, Phase II in MF |
| Celgene | CC-930 | JNK inhibitor | Oral | IPF | Phase II |
| Gilead/Arresto | GS-6624 | Anti-LOXL2 monoclonal antibody | IV | MF, LF, IPF | Phase II in MF, Phase I/II in LF, and Phase I in IPF |
| Amarillo Biosciences | IFN-α | Anti-inflammatory | Oral | IPF | Phase II |
| Wyeth | Etanercept (Enbrel) | Soluble TNF-α receptor | Subcut. | IPF | Phase II |
| Cornerstone Therapeutics/Skyepharma | Zileuton (Zyflo) | Leukotriene synthesis inhibitor, 5-LO inhibitor | Oral | IPF | Phase II |
| Adeona/Pipex Therapeutics | Tetrathiomolybdate (Coprexa) | Copper chelator | Oral | IPF, DN | Phase II |
| Centocor | CNTO-888 | Anti-CCL2 monoclonal antibody | IV | IPF | Phase II |
| Novartis | QAX576 | IL-13 inhibitor | IV | IPF, asthma | Phase II |
| Pharmaxis | PXS25 | Leukocyte extravasation inhibitor | IV | IPF | Phase II |
| Mondobiotech | Vasoactive intestinal peptide | Anti-inflammatory | Inhaled | IPF | Phase II |
| Lilly | LY2382770 | Anti-TGF-β monoclonal antibody | Subcut. | DN | Phase II |
| Genzyme | GC-1008 (fresolimumab) | Anti-TGF-β monoclonal antibody | IV | IPF, MF | Phase II in IPF, Phase I in MF |
| FibroGen | FG-3019 | Anti-CTGF human monoclonal antibody | IV | IPF, DN, LF in HBV | Phase II in IPF, Phase II in DN, Phase II in LF |
| Insys Therapeutics | Cintredekin besudotox | IL-13 receptor+ cell destruction | Inhaled | IPF | Phase II, appears discontinued |
| Stromedix | STX-100 | Anti–αvβ6 integrin monoclonal antibody | IV | IPF | Phase Ib/IIa |
| Promedior | PRM-151 | Recombinant human SAP, monocyte inhibitor | IV | IPF | Phase Ib |
| Bristol-Myers Squibb | — | Anti-IL-4/IL-13 receptor monoclonal antibody | IV | IPF | Phase I |
Abbreviations: CTGF, connective tissue growth factor; DN, diabetic nephropathy; FGFR, fibroblast growth factor receptor; FSGS, focal segmental glomerulsclerosis; IFN, interferon; IL, interleukin; IPF, idiopathic pulmonary fibrosis; IV, intravenous; LF, liver fibrosis; MF, myelofibrosis; PAH, pulmonary arterial hypertension; PDE, phosphodiesterase; PDGFR, platelet-derived growth factor receptor; SAP, serum amyloid protein; subcut., subcutaneous; TGF, transforming growth factor; TNF, tumor necrosis factor; VEGFR, vascular endothelial growth factor receptor; HBV, hepatitis B virus infection.