Etanercept biosimilars
A protein that soaks up TNF, used in rheumatoid and psoriatic arthritis, spondylitis and psoriasis, and approved in the United States since 2016 but not yet sold there.
About etanercept
Etanercept is not an antibody but a fusion protein: the part of a human TNF receptor joined to the tail of an antibody. It acts as a decoy, catching TNF before it reaches the cells that cause inflammation. It was one of the first biologics for arthritis.
TNF drives inflammation in the joints, spine and skin. Etanercept binds it in the blood and holds it there. Because it does not attach firmly to TNF on cell surfaces, it is not used in Crohn's disease, unlike the anti-TNF antibodies.
An injection under the skin once a week, from pre-filled syringes or pens. Some Indian products come as a powder to be made up before injection.
Rheumatoid arthritis, juvenile arthritis, psoriatic arthritis, spondylitis and plaque psoriasis.
Etanercept is one of the harder biologics to copy, because it is a mixture of forms and the biosimilar has to match that mixture, not just the main molecule. Immune reactions are rare and rarely matter. Clinical comparisons are done in rheumatoid arthritis or psoriasis.
The reference product is Enbrel, from Amgen in North America and Pfizer elsewhere. In Europe biosimilars have been sold since 2016. In the United States, patents that run until 2029 have kept both approved biosimilars off the market.
With etanercept, patents rather than science have set the timetable in the United States. Two biosimilars have been approved in the United States since 2016 and neither can launch before 2029. In Europe the first biosimilar took most of the market in several countries. India permitted its first product in 2012, and Lupin's Indian product has since reached Europe under Biocon.
Clinical details are summarised from the reference product's prescribing information. Approval dates, numbers and presentations are in the tables below, each with its source.
Competitive outlook
- Todayseven etanercept biosimilars are approved in at least one of the seven markets.
- Nearest to marketCHS-0214, MB04 have reached phase 3, the last trial before a filing.
- Further outAltebrel is still at the pharmacokinetic stage, usually two to three years from any approval.
- If all of them arriveThe approved count would rise from seven to ten.
8 published switching studies with etanercept biosimilars, 1 of them trials with repeated switching, and where evidence is still missing.
Approvals by year
Regulatory register
| Regulator | Brand | Holder or applicant | Approved | Application or permission | US licence | Status | Source |
|---|---|---|---|---|---|---|---|
| FDA | Erelzi | Sandoz Inc. | Aug 2016 | 761042 | Biosimilar | Approved | S001, S016 |
| FDA | Eticovo | Samsung Bioepis Co., Ltd. | Apr 2019 | 761066 | Interchangeable | Approved | S001, S016 |
| EMA | Benepali | Samsung Bioepis NL B.V. | Jan 2016 | EMEA/H/C/004007 | Approved | S017 | |
| EMA | Erelzi | Sandoz GmbH | Jun 2017 | EMEA/H/C/004192 | Approved | S017 | |
| EMA | Nepexto | Biosimilar Collaborations Ireland Limited | May 2020 | EMEA/H/C/004711 | Approved | S017 | |
| EMA | Fubelv | Biosimilar Collaborations Ireland Limited | Apr 2026 | EMEA/H/C/006738 | Approved | S017 | |
| MHRA | Benepali | Not shown in the MHRA substance list | not shown | not published | Approved | S023 | |
| MHRA | Erelzi | Not shown in the MHRA substance list | not shown | not published | Approved | S023 | |
| MHRA | Nepexto | Not shown in the MHRA substance list | not shown | not published | Approved | S023 | |
| PMDA | Etanercept BS MA | Mochida Pharmaceutical | Jan 2018 | not published | Approved | S020 | |
| PMDA | Etanercept BS TY / Nichiiko | Yoshindo; Nichi-Iko Pharmaceutical | Mar 2019 | not published | Approved | S020 | |
| HC | Brenzys | Samsung Bioepis CO., LTD | Aug 2016 | DIN 02455323, 02455331 | Approved | S022 | |
| HC | Erelzi | Sandoz Canada Incorporated | Apr 2017 | DIN 02462850, 02462869, 02462877 | Approved | S022 | |
| HC | Rymti | Lupin Pharma Canada Limited | Aug 2022 | DIN 02530295, 02530309 | Approved | S022 | |
| CDSCO | Cipla (INN only) | Cipla Limited | Oct 2012 | Import permission | Approved | S013 | |
| CDSCO | Intas Pharmaceuticals (INN only) | Intas Pharmaceuticals Ltd | Sep 2014 | MF-198/2014 | Approved | S014 | |
| CDSCO | Reliance Life Sciences (INN only) | Reliance Life Sciences Pvt Ltd | May 2018 | MF-124/2018 | Approved | S014 | |
| CDSCO | Lupin (INN only) | Lupin Limited | Mar 2019 | MF/BIO/19/000011 | Approved | S014 | |
| CDSCO | Mylan Pharmaceuticals Private (INN only) | Mylan Pharmaceuticals Private Limited, now Biocon Biologics Limited | Jan 2021 | MF/BIO/21/000005 | Approved | S011 | |
| EDE | Erelzi | Novartis Pharmaceutical Manufacturing GmbH (Sandoz) | Apr 2020 | not published | Registered | S018 |
Last checked Sep 2026. US interchangeability designations are listed in full on the interchangeable biosimilars page. CDSCO lists permissions by firm and INN, not brand. PMDA's list and the UAE directory do not publish application numbers; Canadian dates are the first approval or market date recorded in the Drug Product Database.
Regulatory pathway by market
Requirements for an etanercept biosimilar under the guidance in force in September 2026.
| FDA, United States | EMA, European Union | MHRA, United Kingdom | PMDA, Japan | Health Canada | CDSCO, India | EDE, UAE | |
|---|---|---|---|---|---|---|---|
| Legal pathway | Section 351(k) of the Public Health Service Act (BPCIA 2009) | Article 10(4) of Directive 2001/83/EC; centralised procedure is mandatory for biotechnology products | UK marketing authorisation from MHRA. EU approvals in force at the end of 2020 became Great Britain licences automatically; new products since 2021 are approved through reliance on EMA or FDA decisions, and from 2024 through the International Recognition Procedure. Northern Ireland follows EU licences | MHLW approval on PMDA review under the Guideline for Ensuring Quality, Safety and Efficacy of Biosimilars (2009, revised 2020), with Q&A updates in 2024 and 2026 | Notice of Compliance under the Food and Drug Regulations as a biosimilar biologic drug, assessed under Health Canada's guidance on biosimilars (2016, revised 2022 and 2026) | Guidelines on Similar Biologics (CDSCO and DBT, 2016, in force); revised draft published May 2025 | Registration through the Emirates Drug Establishment; the public directory does not distinguish biosimilars from other biologicals |
| Reference product | US-licensed reference; a non-US comparator may be used with analytical and PK bridging | EU-authorised reference; a non-EEA comparator may be used with bridging data | Reference biologic authorised in the UK, or an EU-authorised version with bridging data | The original biopharmaceutical approved in Japan; foreign-sourced reference accepted with bridging since the 2020 revision | Reference biologic drug authorised in Canada, or a non-Canadian version of it with bridging data | Product licensed in India, or if not, one licensed in an ICH country, with justification | Not stated in the public directory; registration relies on assessment by reference regulators |
| Comparative clinical study | Draft guidance (October 2025): comparative analytical assessment plus a PK similarity study and immunogenicity assessment; a comparative efficacy study is generally not needed | Reflection paper adopted March 2026: a comparative efficacy trial can be waived when analytical and PK comparability is sufficient | Follows the EU guideline; MHRA's 2021 biosimilar guidance states that a comparative efficacy trial is generally not needed where analytical and pharmacokinetic comparability is shown | Comparative PK study and, in principle, a comparative efficacy study; the May 2026 early consideration sets out when the efficacy study can be omitted, and Japanese patient data are no longer required in every case (2025) | Comparative structural and functional studies, PK and, where warranted, PD equivalence; the 2026 revision reduces the expectation of comparative efficacy trials in line with FDA and EMA | Comparative PK/PD study and a comparative safety and efficacy study are generally expected, followed by a post-marketing study | Assessed on the dossier accepted by the reference regulator |
| Interchangeability | A separate designation permitting pharmacy-level substitution; switching studies generally not required under the June 2024 draft | EMA and HMA statement (September 2022): EU biosimilars are interchangeable with their reference; substitution rules are set by each member state | No designation; MHRA considers approved biosimilars interchangeable with their reference, and switching is decided by the prescriber and by NHS commissioning | Not defined; prescribing by brand, with pharmacist substitution not automatic | No federal designation; substitution and mandatory switching policies are set by each province, several of which have required switching since 2019 | Not defined in the guidelines | Not defined |
| Naming | INN plus a four-letter suffix | INN, identical to the reference; brand name and batch recorded for pharmacovigilance | Brand name with the non-proprietary name; licence numbers PL, PLGB or PLNI | INN followed by BS (biosimilar), strength, form and the company name in quotation marks, with a biosimilar number in the non-proprietary name | Non-proprietary name identical to the reference, with brand name and DIN as identifiers | INN with the brand name | Brand name as registered |
Sources: FDA draft guidance on comparative efficacy studies (October 2025) and interchangeability (June 2024); EMA reflection paper EMA/CHMP/BMWP/60916/2025 (March 2026) and EMA/HMA statement on interchangeability (September 2022); CDSCO Guidelines on Similar Biologics 2016 and 2025 draft (S009, S010); EDE directory (S018); MHLW/PMDA biosimilar guideline and notifications (S021); Health Canada guidance on biosimilar biologic drugs; MHRA guidance on the licensing of biosimilar products (2021).
EvySaif prepares the comparative evidence plan and the regional dossier strategy for etanercept programmes. Regulatory strategy consulting
Presentations and concentration
Solution presentations are 25 mg/0.5 mL and 50 mg/mL in pre-filled syringes and pens. Lyophilised 25 mg vials exist for some Indian products.
| Product | FDA | EMA | MHRA | PMDA | HC | CDSCO | EDE |
|---|---|---|---|---|---|---|---|
| Erelzi GP2015 | 25 mg vial, 25 mg/0.5 mL, 50 mg/mL syringe and Sensoready pen | see SmPC | 25 mg syringe; 50 mg pen | · | 25, 50 mg | · | 25 mg/0.5 mL, 50 mg/mL |
| Eticovo / Benepali SB4 | 25 mg/0.5 mL, 50 mg/mL | see SmPC | 25 mg syringe; 50 mg syringe and pen | · | 50 mg | · | · |
| Nepexto / Fubelv / Lupin etanercept YLB113 | · | see SmPC | 25 mg syringe; 50 mg syringe and pen | 10 mg, 25 mg and 50 mg syringes; 50 mg pen | 50 mg | 50 mg/mL pen and PFS; 25 mg/0.5 mL PFS; 50 mg/mL and 25 mg/0.5 mL PFS | · |
| Intas etanercept | · | · | · | · | · | 25 mg/0.5 mL PFS | · |
| Reliance Life Sciences etanercept | · | · | · | · | · | 25 mg lyophilised multi-use vial | · |
| Cipla etanercept | · | · | · | · | · | 25 mg lyophilised vial | · |
| Etanercept BS MA LBEC0101 | · | · | · | 10 mg and 25 mg vials; 25 mg/0.5 mL and 50 mg/mL syringes; 25 mg and 50 mg pens | · | · | · |
EU presentations are listed in each product's SmPC.
Developers by market
| Developer | Product | FDA | EMA | MHRA | PMDA | HC | CDSCO | EDE |
|---|---|---|---|---|---|---|---|---|
| Sandoz | Erelzi | ✓ | ✓ | ✓ | · | ✓ | · | ✓ |
| Samsung Bioepis | Eticovo / Benepali | ✓ | ✓ | ✓ | · | ✓ | · | · |
| Lupin | Nepexto / Fubelv / Lupin etanercept | · | ✓ | ✓ | ✓ | ✓ | ✓ | · |
| Intas Pharmaceuticals | Intas etanercept | · | · | · | · | · | ✓ | · |
| Reliance Life Sciences | Reliance Life Sciences etanercept | · | · | · | · | · | ✓ | · |
| Not stated in the CDSCO list | Cipla etanercept | · | · | · | · | · | ✓ | · |
| Mochida Pharmaceutical (LG Chem product) | Etanercept BS MA | · | · | · | ✓ | · | · | · |
Entering a market where a competitor is already listed changes the evidence and pricing conversation. EvySaif's global value dossier and HTA submission work covers that side.
Products
Erelzi
Eticovo / Benepali
Nepexto / Fubelv / Lupin etanercept
Intas etanercept
Reliance Life Sciences etanercept
Cipla etanercept
Etanercept BS MA
In development
ClinicalTrials.gov holds seven comparative trials of five etanercept biosimilar candidates against the reference product, run by five sponsors. Three of the candidates (Altebrel, CHS-0214, MB04) have no approval yet in any of the seven markets, so they show where the next competition may come from. Trials are listed with the sponsor's own wording for status and dates.
| Candidate | Developer or sponsor | Reference product | Phase | Design | Registry status | Started | Primary completion | In the Atlas | Registry record |
|---|---|---|---|---|---|---|---|---|---|
| Altebrel | AryoGen Pharmed | Enbrel | Phase 1 | Comparative PK | Completed | Dec 2016 | Mar 2017 | no approval in the seven markets | NCT03273088 |
| CHS-0214 | Coherus BioSciences | Enbrel | Phase 3 | Comparative efficacy | Completed | May 2014 | Oct 2015 | no approval in the seven markets | NCT02115750 |
| SB4 | Samsung Bioepis | Enbrel | Phase 3 | Comparative efficacy | Completed | Jun 2013 | Apr 2014 | Eticovo / Benepali | NCT01895309 |
| GP2015 | Sandoz | Enbrel | Phase 3 | Comparative efficacy | Completed | Feb 2015 | Dec 2016 | Erelzi | NCT02638259 |
| GP2015 | Sandoz | Enbrel | Phase 3 | Comparative efficacy | Completed | Jun 2013 | Jun 2014 | Erelzi | NCT01891864 |
| MB04 | mAbxience | Enbrel | Phase 1 | Comparative PK | Completed | Mar 2024 | May 2025 | no approval in the seven markets | NCT06392074 |
| MB04 | mAbxience | Enbrel | Phase 3 | Comparative efficacy | Recruiting | Oct 2024 | Oct 2025 | no approval in the seven markets | NCT06596772 |
Registry data from ClinicalTrials.gov, entered by the sponsors and not verified by any regulator. Status and dates are as posted; sponsors often update them late. Trials registered only on other registries, such as India's CTRI or China's ChiCTR, are not included. Checked 12 Sep 2026. The full list across all molecules is on the pipeline page.
Questions
Why is no etanercept biosimilar sold in the United States?
Amgen's patents on etanercept and its manufacture run until 2029, and courts upheld them. Both FDA-approved biosimilars are licensed but cannot launch.
Which was the first etanercept biosimilar?
Cipla's imported product in India in 2012, followed by Intas's domestic product in 2014. Europe's first was Benepali in 2016.
Why is etanercept hard to copy?
It is a mixture of slightly different forms of the same protein, and a biosimilar has to reproduce that mixture as well as the main molecule.
Which etanercept biosimilars are registered in the UAE?
Sandoz's Erelzi, alongside Enbrel.
Is etanercept used in Crohn's disease?
No. Unlike the anti-TNF antibodies, it does not work in bowel disease, so neither the original nor its biosimilars are approved for it.
Which Indian companies make etanercept?
Intas, Reliance and Lupin hold manufacturing permissions, and Cipla imports a product. Lupin's version is also sold in Europe by Biocon.
Work with EvySaif on etanercept
Etanercept biosimilar landscape report
The register on this page as a delivered document: every approval, holder, presentation and pathway requirement across FDA, EMA, CDSCO and the Gulf, updated to the month, with the sources attached.
Request the landscape reportRegulatory gap assessment
For a developer deciding whether and where to file: a review of your analytical, PK and clinical package against what each regulator expects for etanercept, with the gaps ranked and a filing sequence recommended.
About the gap assessmentSources
S001FDA, Biosimilar Product Information (approved biosimilars table) Primary (regulator)S016FDA Purple Book, monthly data downloads January to August 2026 Primary (regulator)S017EMA, medicines data table (medicines-output-medicines-report_en.xlsx) Primary (regulator)S013CDSCO, import and market permissions till 2019 (r-DNA) Primary (regulator)S014CDSCO, permissions granted in Form 46 and 46A, to 2019 Primary (regulator)S011CDSCO, new drugs (r-DNA origin) approved for manufacture and marketing, Jan 2020 to June 2026 (CT-21) Primary (regulator)S018UAE Emirates Drug Establishment, registered medical product directory Primary (regulator)S020PMDA, list of approved biosimilar products in Japan (as of July 2026) Primary (regulator)S022Health Canada, Drug Product Database data extract (active and inactive product files, biosimilar table) Primary (regulator)S023MHRA Products, substance lists of licensed medicines (products.mhra.gov.uk) Primary (regulator)S009CDSCO and DBT, Guidelines on Similar Biologics 2016 Primary (regulator)S010CDSCO, Draft Guidelines on Similar Biologics 2025 Primary (regulator)S024ClinicalTrials.gov, study records (API v2, one query per molecule with the term biosimilar) Registry (sponsor-entered)
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