Chemistry:Avacopan

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Avacopan, sold under the brand name Tavneos, is a medication used to treat anti-neutrophil cytoplasmic autoantibody-associated vasculitis.[1][2][3] Avacopan is a complement 5a receptor antagonist[1] and a cytochrome P450 3A4 inhibitor.[1]

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).[2]

Avacopan was approved for medical use in Japan in September 2021,[4] and in the United States in October 2021.[1][3][5] It is the first orally-administered inhibitor of the complement C5a receptor approved by the US Food and Drug Administration (FDA).[3] The FDA considers it to be a first-in-class medication.[6]

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.[7] 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.[8]

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.[9]

Medical uses

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.[1][10]

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.[2]

History

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.[11] In the clinical trial, participants were randomly assigned to receive avacopan or placebo for 52 weeks.[11] Participants in the placebo group received a glucocorticoid taper over 20 weeks.[11] Neither the participants nor healthcare providers knew which medication was being given.[11] Participants in both groups received background immunosuppressive treatment (cyclophosphamide or rituximab) and were allowed to receive additional glucocorticoids.[11] 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.[11] Data from this trial were also analyzed for the assessment of side effects.[11] The trial was conducted at 143 sites in 18 countries including the United States.[11] This trial assessed both efficacy and safety.[11] 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.[11] The proportion of participants who achieved remission after six months of treatment was similar.[11]

Society and culture

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.[12] The applicant for this medicinal product is Vifor Fresenius Medical Care Renal Pharma France.[12] The EMA considers avacopan to be a first-in-class medicine.[13] Avacopan was approved for medical use in the European Union in January 2022.[2][14]

The US Food and Drug Administration granted the application for avacopan orphan drug designation.[6]

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.[15] The review of Tavneos was initiated at the request of the European Commission, under Article 20 of Regulation (EC) No 726/2004.[16]

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.[17]

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.[18][19]

Names

Avacopan is the international nonproprietary name.[20]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Cite error: Invalid <ref> tag; no text was provided for refs named Tavneos FDA label
  2. ↑ 2.0 2.1 2.2 2.3 "Tavneos EPAR". 10 November 2021. https://www.ema.europa.eu/en/medicines/human/EPAR/tavneos.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  3. ↑ 3.0 3.1 3.2 "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.
  4. ↑ "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.
  5. ↑ "Drug Approval Package: Tavneos". 4 November 2021. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214487Orig1s000TOC.cfm. 
  6. ↑ 6.0 6.1 (PDF) Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (Report). 13 May 2022. https://www.fda.gov/media/155227/download. Retrieved 22 January 2023.  Public Domain This article incorporates text from this source, which is in the public domain.
  7. ↑ Research, Center for Drug Evaluation and (2026-04-03). "FDA Identifies Cases of Serious Liver Injury in Patients Taking Tavneos (avacopan) for Severe Active Anti-neutrophil Cytoplasmic Autoantibody (ANCA)-associated Vasculitis" (in en). FDA. https://www.fda.gov/drugs/drug-safety-communications/fda-identifies-cases-serious-liver-injury-patients-taking-tavneos-avacopan-severe-active-anti. 
  8. ↑ 満武 里奈 (2026-05-16). "Error: no |title= specified when using {{Cite web}}". https://medical.nikkeibp.co.jp/leaf/mem/pub/hotnews/int/202605/593214.html. 
  9. ↑ Research, Center for Drug Evaluation and (2026-04-27). "CDER proposes to withdraw approval of TAVNEOS" (in en). FDA. https://www.fda.gov/drugs/drug-alerts-and-statements/cder-proposes-withdraw-approval-tavneos. 
  10. ↑ "Center for Drug Evaluation and Research - Approval Package for: Application Number: 214487Orig1s000". 7 October 2021. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214487Orig1s000Approv.pdf. 
  11. ↑ 11.00 11.01 11.02 11.03 11.04 11.05 11.06 11.07 11.08 11.09 11.10 "Drug Trials Snapshot: Tavneos". 7 October 2021. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-tavneos.  Public Domain This article incorporates text from this source, which is in the public domain.
  12. ↑ 12.0 12.1 "Tavneos: Pending EC decision". 11 November 2021. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/tavneos.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  13. ↑ "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.
  14. ↑ "Tavneos Product information". https://ec.europa.eu/health/documents/community-register/html/h1605.htm. 
  15. ↑ "EMA starts review of Tavneos, a medicine for rare autoimmune diseases GPA and MPA". 30 January 2026. https://www.ema.europa.eu/en/news/ema-starts-review-tavneos-medicine-rare-autoimmune-diseases-gpa-mpa. 
  16. ↑ "Tavneos - referral". 30 January 2026. https://www.ema.europa.eu/en/medicines/human/referrals/tavneos. 
  17. ↑ "FDA identifies eight deaths tied to Amgen's rare disease drug Tavneos". 1 April 2026. https://endpoints.news/fda-identifies-eight-deaths-tied-to-amgens-tavneos. 
  18. ↑ "ChemoCentryx, Inc.; Proposal To Withdraw Approval of New Drug Application for TAVNEOS (Avacopan) Capsule, 10 Milligrams; Opportunity for a Hearing". https://www.federalregister.gov/documents/2026/04/30/2026-08455/chemocentryx-inc-proposal-to-withdraw-approval-of-new-drug-application-for-tavneos-avacopan-capsule. 
  19. ↑ Lowe, Derek. "The FDA Cracks Down on Tavneos". Science.org. https://www.science.org/content/blog-post/fda-cracks-down-tavneos. 
  20. ↑ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 76". WHO Drug Information 30 (3). 2016. 

Further reading

  • Clinical trial number NCT02994927 for "A Phase 3 Clinical Trial of CCX168 (Avacopan) in Patients With ANCA-Associated Vasculitis (ADVOCATE)" at ClinicalTrials.gov



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