avacopan   Click here for help

GtoPdb Ligand ID: 9450

Synonyms: CCX-168 | CCX168 | Tavneos®
Approved drug PDB Ligand Immunopharmacology Ligand
avacopan is an approved drug (FDA (2021), EMA (2022))
Compound class: Synthetic organic
Comment: Avacopan is a small molecule, competitive and orally bioactive antagonist of human C5a1 receptor [1]. It was originally proposed as an alternative to steroid (glucocorticoid) therapy for ANCA-associated vasculitis [3,7]. The evidence confirming C5, C5a and the C5a receptor as anti-inflammatory and anti-cancer drug targets was reviewed by Horiuchi and Tsukamoto (2016) [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 61.44
Molecular weight 581.27
XLogP 7.52
No. Lipinski's rules broken 1
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Canonical SMILES O=C(C1CCCN(C1c1ccc(cc1)NC1CCCC1)C(=O)c1c(C)cccc1F)Nc1ccc(c(c1)C(F)(F)F)C
Isomeric SMILES O=C([C@H]1CCCN([C@H]1c1ccc(cc1)NC1CCCC1)C(=O)c1c(C)cccc1F)Nc1ccc(c(c1)C(F)(F)F)C
InChI InChI=1S/C33H35F4N3O2/c1-20-12-15-25(19-27(20)33(35,36)37)39-31(41)26-10-6-18-40(32(42)29-21(2)7-5-11-28(29)34)30(26)22-13-16-24(17-14-22)38-23-8-3-4-9-23/h5,7,11-17,19,23,26,30,38H,3-4,6,8-10,18H2,1-2H3,(H,39,41)/t26-,30-/m0/s1
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Summary of Clinical Use Click here for help
Avacopan (research code CCX168) was evaluated in clinical trials for efficacy in ANCA-associated vasculitis and C3 glomerulopathy. Phase 2 results in ANCA-associated vasculitis were reported in [4]. This study showed that avacopan safely and effectively replaced high dose glucocorticoid (prednisolone) therapy in patients with ANCA-associated vasculitis, which supported progression to Phase 3 trial.
The EMA granted orphan designations for avacopan as a treatment for granulomatosis with polyangiitis, microscopic polyangiitis (both 2014), and C3 glomerulopathy (2017).
Positive results from Phase 3 (ADVOCATE trial NCT02994927 [6]) led to FDA approval of avacopan as an adjunct (in combination with standard therapy) for the treatment of severe ANCA-associated vasculitis in October 2021.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03301467 Controlled Trial Evaluating Avacopan in C3 Glomerulopathy Phase 2 Interventional ChemoCentryx
NCT02994927 A Phase 3 Clinical Trial of CCX168 (Avacopan) in Patients With ANCA-Associated Vasculitis Phase 3 Interventional ChemoCentryx 6
NCT01363388 A Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With ANCA-Associated Vasculitis Phase 2 Interventional ChemoCentryx 4