Investigational Drug Details
| Drug ID: | D250 |
| Drug Name: | Odevixibat |
| Synonyms: | A4250; BRAVO-1 |
| Type: | Chemical drug |
| DrugBank ID: | DB16261 |
| DrugBank Description: | Odevixibat, or A4250, is an ileal sodium/bile acid cotransporter inhibitor indicated for the treatment of pruritus in patients older than 3 months, with progressive familiar intrahepatic cholestasis (PFIC). Odevixibat is the first approved non-surgical treatment option for PFIC. Previous therapies for PFIC included a bile acid sequestrant such as . Odevixibat was granted FDA approval on 20 July 2021. |
| PubChem ID: | 10153627 |
| CasNo: | 501692-44-0 |
| Repositioning for NAFLD: | No |
| SMILES: | O=S1(=O)c2c(N(CC(N1)(CCCC)CCCC)c1ccccc1)cc(c(c2)OCC(=O)N[C@@H](C(=O)N[C@H](C(=O)O)CC)c1ccc(cc1)O)SC |
| Structure: |
|
| InChiKey: | XULSCZPZVQIMFM-IPZQJPLYSA-N |
| Molecular Weight: | 740.945 |
| DrugBank Targets: | Ileal sodium/bile acid cotransporter inhibitor |
| DrugBank MoA: | Progressive familiar intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders leading to cholestasis, fibrosis, and eventually a need for liver transplantation. Patients with PFIC require liver transplants or develop hepatocellular carcinomas in their first few years of life. Many of these patients experience severe pruritus. The exact mechanism of pruritus is PFIC is not known, but lower concentrations of bile acids have been shown to reduce pruritus. Patients with certain forms of PFIC type 2, associated with a non-functional or absent bile salt export pump, are not expected to benefit from odevixibat treatment. The ileal sodium/bile acid cotransporter is a transport glycoprotein responsible for reabsorption of 95% of bile acids in the distal ileum. Odevixibat is a reversible inhibitor of the ileal sodium/bile acid contransporter. Patients taking odevixibat for a week experienced a 56% reduction in bile acid area under the curve with a 3 mg once daily dose. A 1.5 mg daily dose lead to a 43% reduction in bile acid area under the curve. The decreased reabsorption of bile acids, leads to reduced stimulation of FXR, which reduces expression of FGF19, reducing binding of FGF19 to FGF4R, decreasing inhibition of bile acid synthesis. Further synthesis of bile acids that will not be reabsorbed in the intestine contributes to lowering low density lipoprotein levels. |
| DrugBank Pharmacology: | Odevixibat, or A4250, is an ileal sodium/bile acid cotransporter inhibitor indicated for the treatment of pruritus in patients older than 3 months, with progressive familiar intrahepatic cholestasis (PFIC). It has a moderate duration of action as it is given once daily. Odevixibat has a wide therapeutic index as patients were given single doses up to 10 mg while the maximum therapeutic dose is 6 mg daily. Patients should be counselled regarding the risks of elevated liver function tests, diarrhea, and fat soluble vitamin defiencies. |
| DrugBank Indication: | Odevixibat is indicated for the treatment of pruritus in patients older than 3 months, with progressive familiar intrahepatic cholestasis (PFIC). It may not be effective in PFIC type 2 with ABCB11 variants. These patients lack a functional bile salt export pump. |
| Targets: | SLC10A2 inhibitor; ASBT inhibitor |
| Therapeutic Category: | -- |
| Clinical Trial Progress: | Phase 2 withdrawn (NCT03451279) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted |
|---|
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T17 | Farnesoid X-activated receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | Details |
| T29 | Fibroblast growth factor 19 | FGF19 | variant | Secreted | O95750 | FGF19_HUMAN | Details |
| T07 | Bile acid receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S10 | Liver transplantation | -- | -- | -- | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Article ID | PMID | Source | Title |
|---|