Avacopan

{{Short description|Chemical compound}} {{Use American English|date=October 2021}} {{Use dmy dates|date=December 2023}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Infobox drug | image = Avacopan structure.svg | image_class = skin-invert-image | width = 250px | alt = | caption =

| pronounce = | tradename = Tavneos | Drugs.com = {{drugs.com|monograph|avacopan}} | MedlinePlus = a622023 | DailyMedID = Avacopan | pregnancy_AU = D | pregnancy_AU_comment = <ref name="Tavneos APMDS">{{Cite web |url=https://www.tga.gov.au/resources/auspmd/tavneos |title=Tavneos {{pipe}} Therapeutic Goods Administration (TGA) |access-date=2 January 2024 |archive-date=2 January 2024 |archive-url=https://web.archive.org/web/20240102022434/https://www.tga.gov.au/resources/auspmd/tavneos |url-status=live }}</ref> | pregnancy_category= | routes_of_administration = By mouth | class = Complement C5a receptor antagonist | ATC_prefix = L04 | ATC_suffix = AJ05 | ATC_supplemental =

| legal_AU = S4 | legal_AU_comment = <ref name="Tavneos APMDS" /><ref>{{cite web | title=Tavneos (Vifor Pharma Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=16 February 2023 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/tavneos-vifor-pharma-pty-ltd | access-date=29 April 2023 | archive-date=27 March 2023 | archive-url=https://web.archive.org/web/20230327062343/https://www.tga.gov.au/resources/prescription-medicines-registrations/tavneos-vifor-pharma-pty-ltd | url-status=live }}</ref> | legal_BR =  | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = <ref>{{cite web | title=Summary Basis of Decision - Tavneos | website=Health Canada | date=28 July 2022 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00597&lang=en | access-date=29 September 2022 | archive-date=29 September 2022 | archive-url=https://web.archive.org/web/20220929050351/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00597&lang=en | url-status=live }}</ref> | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK = POM | legal_UK_comment = <ref>{{cite web | title=Tavneos (Avacopan) Summary of Product Characteristics (SmPC) | website=emc | date=26 May 2022 | url=https://www.medicines.org.uk/emc/product/13744/smpc | access-date=23 July 2023 | archive-date=24 July 2023 | archive-url=https://web.archive.org/web/20230724001757/https://www.medicines.org.uk/emc/product/13744/smpc | url-status=live }}</ref> | legal_US = Rx-only | legal_US_comment = <ref name="Tavneos FDA label">{{cite web | title=Tavneos- avacopan capsule | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c93cbc0b-29a3-46a5-9c85-41815ea5cf4a | access-date=31 October 2021 | archive-date=1 November 2021 | archive-url=https://web.archive.org/web/20211101041949/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c93cbc0b-29a3-46a5-9c85-41815ea5cf4a | url-status=live }}</ref> | legal_EU = Rx-only | legal_EU_comment = <ref name="Tavneos EPAR" /> | legal_UN =  | legal_UN_comment = | legal_status = Rx-only<ref name="ChemoCentryx PR 20210927" />

| IUPAC_name = (2''R'',3''S'')-2-{4-[(cyclopentyl)amino]phenyl}-1-(2-fluoro-6-methylbenzoyl)-''N''-(3-(trifluoromethyl)-4-methylphenyl)piperidine-3-carboxamide | C = 33 | H = 35 | F = 4 | N = 3 | O = 2 | SMILES = Cc1ccc(NC(=O)[C@H]2CCCN(C(=O)c3c(C)cccc3F)[C@H]2c2ccc(NC3CCCC3)cc2)cc1C(F)(F)F | StdInChI = 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 | StdInChI_comment = | StdInChIKey = PUKBOVABABRILL-YZNIXAGQSA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }}

'''Avacopan''', sold under the brand name '''Tavneos''', is a medication used to treat anti-neutrophil cytoplasmic autoantibody-associated vasculitis.<ref name="Tavneos FDA label" /><ref name="Tavneos EPAR" /><ref name="ChemoCentryx PR">{{cite press release | title=ChemoCentryx Announces FDA Approval of Tavneos (avacopan) in ANCA-Associated Vasculitis | website=ChemoCentryx, Inc. | date=8 October 2021 | url=https://ir.chemocentryx.com/news-releases/news-release-details/chemocentryx-announces-fda-approval-tavneostm-avacopan-anca | access-date=11 October 2021 | archive-date=8 October 2021 | archive-url=https://web.archive.org/web/20211008203634/https://ir.chemocentryx.com/news-releases/news-release-details/chemocentryx-announces-fda-approval-tavneostm-avacopan-anca | url-status=live }}</ref> Avacopan is a complement 5a receptor antagonist<ref name="Tavneos FDA label" /> and a cytochrome P450 3A4 inhibitor.<ref name="Tavneos FDA label" />

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).<ref name="Tavneos EPAR" />

Avacopan was approved for medical use in Japan in September 2021,<ref name="ChemoCentryx PR 20210927">{{cite press release | title=ChemoCentryx Announces Approval in Japan of Tavneos (Avacopan) for the Treatment of ANCA-Associated Vasculitis | website=ChemoCentryx, Inc. | date=27 September 2021 | url=https://ir.chemocentryx.com/news-releases/news-release-details/chemocentryx-announces-approval-japan-tavneostm-avacopan | access-date=11 October 2021 | archive-date=9 October 2021 | archive-url=https://web.archive.org/web/20211009005211/https://ir.chemocentryx.com/news-releases/news-release-details/chemocentryx-announces-approval-japan-tavneostm-avacopan | url-status=live }}</ref> and in the United States in October 2021.<ref name="Tavneos FDA label" /><ref name="ChemoCentryx PR" /><ref>{{cite web | title=Drug Approval Package: Tavneos | website=U.S. Food and Drug Administration (FDA) | date=4 November 2021 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214487Orig1s000TOC.cfm | access-date=7 May 2022 | archive-date=7 May 2022 | archive-url=https://web.archive.org/web/20220507191220/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214487Orig1s000TOC.cfm }}</ref> It is the first orally-administered inhibitor of the complement C5a receptor approved by the US Food and Drug Administration (FDA).<ref name="ChemoCentryx PR" /> The FDA considers it to be a first-in-class medication.<ref name="New Drug Therapy Approvals 2021">{{cite report | title=Advancing Health Through Innovation: New Drug Therapy Approvals 2021 | website=U.S. Food and Drug Administration (FDA) | date=13 May 2022 | url=https://www.fda.gov/media/155227/download | format=PDF | access-date=22 January 2023 | archive-date=6 December 2022 | archive-url=https://web.archive.org/web/20221206210020/https://www.fda.gov/media/155227/download }} {{PD-notice}}</ref>

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.<ref>{{Cite journal |last=Research |first=Center for Drug Evaluation and |date=2026-04-03 |title=FDA Identifies Cases of Serious Liver Injury in Patients Taking Tavneos (avacopan) for Severe Active Anti-neutrophil Cytoplasmic Autoantibody (ANCA)-associated Vasculitis |url=https://www.fda.gov/drugs/drug-safety-communications/fda-identifies-cases-serious-liver-injury-patients-taking-tavneos-avacopan-severe-active-anti |journal=FDA |language=en}}</ref> 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.<ref>{{Cite web |author=満武里奈 |date=2026-05-16 |script-title=ja: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 |url=https://medical.nikkeibp.co.jp/leaf/mem/pub/hotnews/int/202605/593214.html |access-date=2026-05-17 |script-website=ja:日経メディカル}}</ref>

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.<ref>{{Cite journal |last=Research |first=Center for Drug Evaluation and |date=2026-04-27 |title=CDER proposes to withdraw approval of TAVNEOS |url=https://www.fda.gov/drugs/drug-alerts-and-statements/cder-proposes-withdraw-approval-tavneos |journal=FDA |language=en}}</ref>

== 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.<ref name="Tavneos FDA label" /><ref>{{Cite web |date=7 October 2021 |title=Center for Drug Evaluation and Research - Approval Package for: Application Number: 214487Orig1s000 |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214487Orig1s000Approv.pdf |archive-url=https://web.archive.org/web/20220507191219/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214487Orig1s000Approv.pdf |archive-date=7 May 2022 |website=U.S. Food and Drug Administration (FDA) }}</ref>

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.<ref name="Tavneos EPAR" />

== 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.<ref name="Tavneos FDA snapshot" /> In the clinical trial, participants were randomly assigned to receive avacopan or placebo for 52 weeks.<ref name="Tavneos FDA snapshot" /> Participants in the placebo group received a glucocorticoid taper over 20 weeks.<ref name="Tavneos FDA snapshot" /> Neither the participants nor healthcare providers knew which medication was being given.<ref name="Tavneos FDA snapshot" /> Participants in both groups received background immunosuppressive treatment (cyclophosphamide or rituximab) and were allowed to receive additional glucocorticoids.<ref name="Tavneos FDA snapshot" /> 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.<ref name="Tavneos FDA snapshot" /> Data from this trial were also analyzed for the assessment of side effects.<ref name="Tavneos FDA snapshot" /> The trial was conducted at 143 sites in 18 countries including the United States.<ref name="Tavneos FDA snapshot" /> This trial assessed both efficacy and safety.<ref name="Tavneos FDA snapshot" /> 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.<ref name="Tavneos FDA snapshot" /> The proportion of participants who achieved remission after six months of treatment was similar.<ref name="Tavneos FDA snapshot">{{cite web | title=Drug Trials Snapshot: Tavneos | website=U.S. Food and Drug Administration (FDA) | date=7 October 2021 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-tavneos | access-date=23 July 2023 | archive-date=23 July 2023 | archive-url=https://web.archive.org/web/20230723204524/https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-tavneos }} {{PD-notice}}</ref>

==Society and culture== === Legal status === 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.<ref name="Tavneos: Pending EC decision" /> The applicant for this medicinal product is Vifor Fresenius Medical Care Renal Pharma France.<ref name="Tavneos: Pending EC decision">{{cite web | title=Tavneos: Pending EC decision | website=European Medicines Agency | date=11 November 2021 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/tavneos | access-date=12 November 2021 | archive-date=12 November 2021 | archive-url=https://web.archive.org/web/20211112122704/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/tavneos | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> The EMA considers avacopan to be a first-in-class medicine.<ref>{{cite press release | title=First-in-class medicine recommended for treatment of rare blood vessel inflammation | website=European Medicines Agency | date=12 November 2021 | url=https://www.ema.europa.eu/en/news/first-class-medicine-recommended-treatment-rare-blood-vessel-inflammation | access-date=12 November 2021 | archive-date=12 November 2021 | archive-url=https://web.archive.org/web/20211112122545/https://www.ema.europa.eu/en/news/first-class-medicine-recommended-treatment-rare-blood-vessel-inflammation | url-status=live }}</ref> Avacopan was approved for medical use in the European Union in January 2022.<ref name="Tavneos EPAR">{{cite web | title=Tavneos EPAR | website=European Medicines Agency | date=10 November 2021 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/tavneos | access-date=24 April 2022 | archive-date=17 March 2022 | archive-url=https://web.archive.org/web/20220317090750/https://www.ema.europa.eu/en/medicines/human/EPAR/tavneos | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref>{{cite web | title=Tavneos Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1605.htm | access-date=3 March 2023 | archive-date=4 March 2023 | archive-url=https://web.archive.org/web/20230304093743/https://ec.europa.eu/health/documents/community-register/html/h1605.htm | url-status=live }}</ref>

The US Food and Drug Administration granted the application for avacopan orphan drug designation.<ref name="New Drug Therapy Approvals 2021"/>

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.<ref>{{cite web | title=EMA starts review of Tavneos, a medicine for rare autoimmune diseases GPA and MPA | website=European Medicines Agency (EMA) | date=30 January 2026 | url=https://www.ema.europa.eu/en/news/ema-starts-review-tavneos-medicine-rare-autoimmune-diseases-gpa-mpa | access-date=17 February 2026}}</ref> The review of Tavneos was initiated at the request of the European Commission, under Article 20 of Regulation (EC) No 726/2004.<ref>{{cite web | title= Tavneos - referral | website=European Medicines Agency (EMA) | date=30 January 2026 | url=https://www.ema.europa.eu/en/medicines/human/referrals/tavneos | access-date=17 February 2026}}</ref>

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.<ref>{{cite web | title= FDA identifies eight deaths tied to Amgen's rare disease drug Tavneos | website=European Medicines Agency (EMA) | date=1 April 2026 | url=https://endpoints.news/fda-identifies-eight-deaths-tied-to-amgens-tavneos | access-date=1 April 2026}}</ref>

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.<ref>{{cite web |title=ChemoCentryx, Inc.; Proposal To Withdraw Approval of New Drug Application for TAVNEOS (Avacopan) Capsule, 10 Milligrams; Opportunity for a Hearing |url=https://www.federalregister.gov/documents/2026/04/30/2026-08455/chemocentryx-inc-proposal-to-withdraw-approval-of-new-drug-application-for-tavneos-avacopan-capsule |website=Federal Register |access-date=1 May 2026}}</ref><ref>{{cite web |last1=Lowe |first1=Derek |title=The FDA Cracks Down on Tavneos |url=https://www.science.org/content/blog-post/fda-cracks-down-tavneos |website=In the pipeline |publisher=Science.org |access-date=1 May 2026}}</ref>

=== Names === Avacopan is the international nonproprietary name.<ref>{{cite journal | year=2016 | title=International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 76 | journal=WHO Drug Information | volume=30 | issue=3 | page= | hdl=10665/331020 | hdl-access=free }}</ref>

== References == {{reflist}}

== Further reading == * {{cite journal |vauthors=Jayne DR, Bruchfeld AN, Harper L, Schaier M, Venning MC, Hamilton P, Burst V, Grundmann F, Jadoul M, Szombati I, Tesař V, Segelmark M, Potarca A, Schall TJ, Bekker P |title=Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis |journal=J Am Soc Nephrol |volume=28 |issue=9 |pages=2756–2767 |date=September 2017 |pmid=28400446 |pmc=5576933 |doi=10.1681/ASN.2016111179 | doi-access=free | title-link=doi }} * {{cite journal |vauthors=Jayne DR, Merkel PA, Schall TJ, Bekker P |title=Avacopan for the Treatment of ANCA-Associated Vasculitis |journal=N Engl J Med |volume=384 |issue=7 |pages=599–609 |date=February 2021 |pmid=33596356 |doi=10.1056/NEJMoa2023386 | doi-access=free | title-link=doi |hdl=11370/c0ae6f1d-6df5-4d0a-83c7-ee4af12b9820 |hdl-access=free }} * {{cite journal |vauthors=Merkel PA, Jayne DR, Wang C, Hillson J, Bekker P |title=Evaluation of the Safety and Efficacy of Avacopan, a C5a Receptor Inhibitor, in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Treated Concomitantly With Rituximab or Cyclophosphamide/Azathioprine: Protocol for a Randomized, Double-Blind, Active-Controlled, Phase 3 Trial |journal=JMIR Res Protoc |volume=9 |issue=4 |article-number=e16664 |date=April 2020 |pmid=32088663 |pmc=7175182 |doi=10.2196/16664 | doi-access=free | title-link=doi }} * {{cite journal |vauthors=Merkel PA, Niles J, Jimenez R, Spiera RF, Rovin BH, Bomback A, Pagnoux C, Potarca A, Schall TJ, Bekker P |title=Adjunctive Treatment With Avacopan, an Oral C5a Receptor Inhibitor, in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis |journal=ACR Open Rheumatol |volume=2 |issue=11 |pages=662–671 |date=November 2020 |pmid=33128347 |pmc=7672305 |doi=10.1002/acr2.11185 | doi-access=free | title-link=doi }}

== External links == * {{ClinicalTrialsGov|NCT02994927|A Phase 3 Clinical Trial of CCX168 (Avacopan) in Patients With ANCA-Associated Vasculitis (ADVOCATE)}}

Category:Immunosuppressants Category:Orphan drugs Category:Fluoroarenes Category:Trifluoromethyl compounds Category:Amides Category:Anilines Category:Piperidines Category:Cyclopentyl compounds