Wikipedia

Avacopan

(Redirected from Tavneos)

Avacopan, sold under the brand name Tavneos, is a medication used to treat anti-neutrophil cytoplasmic autoantibody-associated vasculitis.[5][6][8] Avacopan is a complement 5a receptor antagonist[5] and a cytochrome P450 3A4 inhibitor.[5]

Avacopan
Clinical data
Trade namesTavneos
Other namesCCX168
AHFS/Drugs.comMonograph
MedlinePlusa622023
License data
Pregnancy
category
Routes of
administration		By mouth
Drug classComplement C5a receptor antagonist
ATC code
Legal status
Legal status
Identifiers
  • (2R,3S)-2-{4-[(cyclopentyl)amino]phenyl}-1-(2-fluoro-6-methylbenzoyl)-N-(3-(trifluoromethyl)-4-methylphenyl)piperidine-3-carboxamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.351.344 Edit this at Wikidata
Chemical and physical data
FormulaC33H35F4N3O2
Molar mass581.656 g·mol−1
3D model (JSmol)
  • Cc1ccc(NC(=O)[C@H]2CCCN(C(=O)c3c(C)cccc3F)[C@H]2c2ccc(NC3CCCC3)cc2)cc1C(F)(F)F
  • 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
  • Key:PUKBOVABABRILL-YZNIXAGQSA-N

The most common side effects include nausea (feeling sick), headache, decrease in white blood cell count, upper respiratory tract (nose and throat) infection, diarrhea, vomiting, and nasopharyngitis (inflammation of the nose and throat).[6]

Avacopan was approved for medical use in Japan in September 2021,[7] and in the United States in October 2021.[5][8][9] It is the first orally-administered inhibitor of the complement C5a receptor approved by the US Food and Drug Administration (FDA).[8] The FDA considers it to be a first-in-class medication.[10]

Since early 2026, avacopan has been reported to have severe side effects, namely drug-induced liver injury (DILI) that involves destruction of intrahepatic small bile ducts, also known as vanishing bile duct syndrome (VBDS). US FDA has identified 76 patients with DILI, of which 56 required hospitalization, and 7 patients passed away.[11] Japan manufacturer Kissei Pharmaceutical also prompts to stop prescribe avacopan, as 20 deaths have been reported in all 8503 Japanese patients due to its side effect.[12]

FDA CDER has proposed a withdrawal of this medication on April 27, 2026, in conjunction with the safety issue, citing a recent discovery in manipulation of phase 3 trial endpoint results that made the medication statistically significant in effectiveness, while the original analysis did not support this conclusion. Currently avacopan remains on the market, until the manufacturer decides to withdrawal, or FDA commissioner mandates the removal of the drug from the market.[13]

Medical uses

edit

In the United States, avacopan is indicated as an adjunctive treatment of adults with severe active anti-neutrophil cytoplasmic autoantibody-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis) in combination with standard therapy including glucocorticoids.[5][14]

In the European Union, avacopan, in combination with a rituximab or cyclophosphamide regimen, is indicated for the treatment of adults with severe, active granulomatosis with polyangiitis or microscopic polyangiitis.[6]

History

edit

Avacopan (ChemoCentryx code name: CCX168) was discovered and developed by ChemoCentryx Inc., a California-based biotech company, which was acquired by Amgen in 2022, one year after the FDA approval of TAVNEOS (avacopan).

The FDA approved avacopan based on evidence from a clinical trial of 330 participants with severe active anti-neutrophil cytoplasmic autoantibody-associated vasculitis.[15] In the clinical trial, participants were randomly assigned to receive avacopan or placebo for 52 weeks.[15] Participants in the placebo group received a glucocorticoid taper over 20 weeks.[15] Neither the participants nor healthcare providers knew which medication was being given.[15] Participants in both groups received background immunosuppressive treatment (cyclophosphamide or rituximab) and were allowed to receive additional glucocorticoids.[15] The benefit of avacopan in comparison to placebo was assessed by proportion of participants who achieved remission at week 26 and sustained remission at week 52.[15] Data from this trial were also analyzed for the assessment of side effects.[15] The trial was conducted at 143 sites in 18 countries including the United States.[15] This trial assessed both efficacy and safety.[15] In the clinical trial, a greater proportion of participants who received avacopan for one year with other medicines (including glucocorticoids) achieved sustained disease remission compared to participants who received other medicines without avacopan.[15] The proportion of participants who achieved remission after six months of treatment was similar.[15]

Society and culture

edit
edit

In November 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Tavneos, intended, in combination with a rituximab or cyclophosphamide regimen, for the treatment of adults with severe, active granulomatosis with polyangiitis or microscopic polyangiitis.[16] The applicant for this medicinal product is Vifor Fresenius Medical Care Renal Pharma France.[16] The EMA considers avacopan to be a first-in-class medicine.[17] Avacopan was approved for medical use in the European Union in January 2022.[6][18]

The US Food and Drug Administration granted the application for avacopan orphan drug designation.[10]

In January 2026, the CHMP started a review of Tavneos following emerging information that raises questions regarding the data integrity of the main study supporting the medicine's marketing authoriaztion in the EU.[19] The review of Tavneos was initiated at the request of the European Commission, under Article 20 of Regulation (EC) No 726/2004.[20]

In 2026, following post-marketing analysis and review, there are reports of 76 DILI injuries and 8 deaths potentially linked to the drug, biopsy confirming the presence of vanishing bile duct syndrome in seven cases.[21]

In April 2026 The US Food and Drug Administration announced intent to withdraw approval of Tavneos due to irregularities in clinical trials and material untruths in the application.[22][23]

Names

edit

References

edit
  1. 1 2 "Tavneos | Therapeutic Goods Administration (TGA)". Archived from the original on 2 January 2024. Retrieved 2 January 2024.
  2. ↑ "Tavneos (Vifor Pharma Pty Ltd)". Therapeutic Goods Administration (TGA). 16 February 2023. Archived from the original on 27 March 2023. Retrieved 29 April 2023.
  3. ↑ "Summary Basis of Decision - Tavneos". Health Canada. 28 July 2022. Archived from the original on 29 September 2022. Retrieved 29 September 2022.
  4. ↑ "Tavneos (Avacopan) Summary of Product Characteristics (SmPC)". emc. 26 May 2022. Archived from the original on 24 July 2023. Retrieved 23 July 2023.
  5. 1 2 3 4 5 6 "Tavneos- avacopan capsule". DailyMed. Archived from the original on 1 November 2021. Retrieved 31 October 2021.
  6. 1 2 3 4 5 "Tavneos EPAR". European Medicines Agency. 10 November 2021. Archived from the original on 17 March 2022. Retrieved 24 April 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  7. 1 2 "ChemoCentryx Announces Approval in Japan of Tavneos (Avacopan) for the Treatment of ANCA-Associated Vasculitis". ChemoCentryx, Inc. (Press release). 27 September 2021. Archived from the original on 9 October 2021. Retrieved 11 October 2021.
  8. 1 2 3 "ChemoCentryx Announces FDA Approval of Tavneos (avacopan) in ANCA-Associated Vasculitis". ChemoCentryx, Inc. (Press release). 8 October 2021. Archived from the original on 8 October 2021. Retrieved 11 October 2021.
  9. ↑ "Drug Approval Package: Tavneos". U.S. Food and Drug Administration (FDA). 4 November 2021. Archived from the original on 7 May 2022. Retrieved 7 May 2022.
  10. 1 2 Advancing Health Through Innovation: New Drug Therapy Approvals 2021. U.S. Food and Drug Administration (FDA) (Report). 13 May 2022. Archived from the original (PDF) on 6 December 2022. Retrieved 22 January 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  11. ↑ Research Cf (3 April 2026). "FDA Identifies Cases of Serious Liver Injury in Patients Taking Tavneos (avacopan) for Severe Active Anti-neutrophil Cytoplasmic Autoantibody (ANCA)-associated Vasculitis". FDA.
  12. ↑ 満武 里奈 (16 May 2026). アバコパン服用により国内で20人死亡、新規患者への使用控えを呼び掛け. 日経メディカル. Retrieved 17 May 2026.
  13. ↑ Research Cf (27 April 2026). "CDER proposes to withdraw approval of TAVNEOS". FDA.
  14. ↑ "Center for Drug Evaluation and Research - Approval Package for: Application Number: 214487Orig1s000" (PDF). U.S. Food and Drug Administration (FDA). 7 October 2021. Archived from the original (PDF) on 7 May 2022.
  15. 1 2 3 4 5 6 7 8 9 10 11 "Drug Trials Snapshot: Tavneos". U.S. Food and Drug Administration (FDA). 7 October 2021. Archived from the original on 23 July 2023. Retrieved 23 July 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  16. 1 2 "Tavneos: Pending EC decision". European Medicines Agency. 11 November 2021. Archived from the original on 12 November 2021. Retrieved 12 November 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  17. ↑ "First-in-class medicine recommended for treatment of rare blood vessel inflammation". European Medicines Agency (Press release). 12 November 2021. Archived from the original on 12 November 2021. Retrieved 12 November 2021.
  18. ↑ "Tavneos Product information". Union Register of medicinal products. Archived from the original on 4 March 2023. Retrieved 3 March 2023.
  19. ↑ "EMA starts review of Tavneos, a medicine for rare autoimmune diseases GPA and MPA". European Medicines Agency (EMA). 30 January 2026. Retrieved 17 February 2026.
  20. ↑ "Tavneos - referral". European Medicines Agency (EMA). 30 January 2026. Retrieved 17 February 2026.
  21. ↑ "FDA identifies eight deaths tied to Amgen's rare disease drug Tavneos". European Medicines Agency (EMA). 1 April 2026. Retrieved 1 April 2026.
  22. ↑ "ChemoCentryx, Inc.; Proposal To Withdraw Approval of New Drug Application for TAVNEOS (Avacopan) Capsule, 10 Milligrams; Opportunity for a Hearing". Federal Register. Retrieved 1 May 2026.
  23. ↑ Lowe D. "The FDA Cracks Down on Tavneos". In the pipeline. Science.org. Retrieved 1 May 2026.
  24. ↑ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 76". WHO Drug Information. 30 (3). 2016. hdl:10665/331020.

Further reading

edit
edit
  • Clinical trial number NCT02994927 for "A Phase 3 Clinical Trial of CCX168 (Avacopan) in Patients With ANCA-Associated Vasculitis (ADVOCATE)" at ClinicalTrials.gov
Retrieved from "https://en.wikipedia.org/w/index.php?title=Avacopan&oldid=1354621871"