Darbepoetin alfa biosimilars
Long-acting erythropoiesis-stimulating agent for renal and chemotherapy anaemia, with biosimilars in India and Japan but none in the United States or European Union.
About darbepoetin alfa
A hyperglycosylated analogue of erythropoietin in which five amino acid substitutions create two additional N-linked glycosylation sites, giving five N-glycans instead of three and a mass of about 37 kDa, produced in Chinese hamster ovary cells.
Binds the erythropoietin receptor on erythroid progenitors with lower affinity than epoetin but much longer residence in the circulation, so the net stimulus to red cell production per dose is greater and dosing can be extended to every one to four weeks.
Half-life about three times that of epoetin, roughly 49 hours intravenously and 73 hours subcutaneously, with bioavailability of about 37% by the subcutaneous route. Dosing once weekly, fortnightly or monthly depending on the indication and the phase of treatment.
0.45 micrograms per kg weekly or 0.75 micrograms per kg fortnightly for renal anaemia, titrated to haemoglobin, from pre-filled syringes of 10 to 500 micrograms; 500 micrograms every three weeks for chemotherapy-induced anaemia.
- Anaemia of chronic kidney disease, in dialysis and pre-dialysis patients
- Chemotherapy-induced anaemia in non-myeloid malignancies
Neutralising antibodies causing pure red cell aplasia are the concern common to all erythropoiesis-stimulating agents. Comparative programmes use analytical similarity with emphasis on the five-glycan profile, pharmacokinetic and pharmacodynamic studies in healthy volunteers, and comparative efficacy in renal anaemia, as the Japanese and Indian approvals show.
Aranesp was licensed by FDA on 17 September 2001 (BLA 103951) and authorised in the EU on 8 June 2001 (EMEA/H/C/000332); in Japan it is marketed by Kyowa Kirin as Nesp. No biosimilar has been filed in the United States or authorised in the EU, where the epoetin biosimilars and the shift to longer-acting agents left little room. India's Dr. Reddy's received the first permission in the world in March 2010, and Japan approved three biosimilars on the same day in September 2019.
Sources: Purple Book (S016), EMA medicines data (S017), CDSCO Form 46 list (S014), PMDA list (S020).
Darbepoetin is the clearest case of a biosimilar market that exists only in Asia: three Indian manufacturers since 2010, three Japanese approvals in 2019, and nothing in the West. For an Indian developer it is a domestic and regional product, and Japan is the one export market with a defined path.
Sources: Aranesp summary of product characteristics (EMA) and US prescribing information (FDA).
Approvals by year
Regulatory register
| Regulator | Brand | Holder or applicant | Approved | Application or permission | US licence | Status | Source |
|---|---|---|---|---|---|---|---|
| PMDA | Darbepoetin Alfa BS [JCR] | JCR Pharmaceuticals | Sep 2019 | not published | Approved | S020 | |
| PMDA | Darbepoetin Alfa BS Sanwa | Sanwa Kagaku Kenkyusho | Sep 2019 | not published | Approved | S020 | |
| PMDA | Darbepoetin Alfa BS MYL | Mylan | Sep 2019 | not published | Approved | S020 | |
| CDSCO | Dr. Reddy's Laboratories (INN only) | Dr. Reddy's Laboratories Ltd | Mar 2010 | MF-246/10 | Approved | S014 | |
| CDSCO | Hetero Drugs (INN only) | Hetero Drugs Limited | Jan 2014 | MF-296/2013 | Approved | S014 | |
| CDSCO | Reliance Life Sciences (INN only) | Reliance Life Sciences Pvt Ltd | Jun 2016 | MF-91/2016 | Approved | S014 |
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 a darbepoetin alfa biosimilar under the guidance in force in September 2026.
| FDA, United States | EMA, European Union | 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 | 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 | 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 | 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 | 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 | 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.
EvySaif prepares the comparative evidence plan and the regional dossier strategy for darbepoetin alfa programmes. Regulatory strategy consulting
Presentations and concentration
Pre-filled syringes from 5 or 10 micrograms to 500 micrograms; Japanese biosimilars span 5 to 180 micrograms.
| Product | FDA | EMA | PMDA | HC | CDSCO | EDE |
|---|---|---|---|---|---|---|
| Dr. Reddy's darbepoetin alfa | · | · | · | · | Injection | · |
| Hetero darbepoetin alfa | · | · | · | · | Injection | · |
| Reliance Life Sciences darbepoetin alfa | · | · | · | · | Injection | · |
| Darbepoetin Alfa BS JCR | · | · | 5 to 180 microgram syringes | · | · | · |
| Darbepoetin Alfa BS Sanwa | · | · | 5 to 180 microgram syringes | · | · | · |
| Darbepoetin Alfa BS MYL | · | · | 5 to 180 microgram syringes | · | · | · |
Sources: Purple Book (S016), PMDA list (S020), Health Canada Drug Product Database (S022), CDSCO permission lists (S011 to S014), EDE directory (S018). EU presentations are listed in each product's SmPC.
Developers by market
| Developer | Product | FDA | EMA | PMDA | HC | CDSCO | EDE |
|---|---|---|---|---|---|---|---|
| Dr. Reddy's Laboratories | Dr. Reddy's darbepoetin alfa | · | · | · | · | ✓ | · |
| Hetero Drugs | Hetero darbepoetin alfa | · | · | · | · | ✓ | · |
| Reliance Life Sciences | Reliance Life Sciences darbepoetin alfa | · | · | · | · | ✓ | · |
| JCR Pharmaceuticals | Darbepoetin Alfa BS JCR | · | · | ✓ | · | · | · |
| Sanwa Kagaku Kenkyusho | Darbepoetin Alfa BS Sanwa | · | · | ✓ | · | · | · |
| Mylan (Viatris) | Darbepoetin Alfa BS MYL | · | · | ✓ | · | · | · |
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
Dr. Reddy's darbepoetin alfa
Hetero darbepoetin alfa
Reliance Life Sciences darbepoetin alfa
Darbepoetin Alfa BS JCR
Darbepoetin Alfa BS Sanwa
Darbepoetin Alfa BS MYL
Questions
Is there a darbepoetin alfa biosimilar in the United States or the European Union?
No. As of September 2026 none has been approved by FDA or authorised by EMA.
Which was the first darbepoetin alfa biosimilar in the world?
Dr. Reddy's product, permitted by CDSCO in March 2010 (MF-246/10).
Is there a darbepoetin alfa biosimilar approved in India?
Yes, three: Dr. Reddy's (March 2010), Hetero (January 2014) and Reliance Life Sciences (June 2016).
Which darbepoetin alfa biosimilars are approved in Japan?
Three, all approved on 20 September 2019: JCR Pharmaceuticals, Sanwa Kagaku Kenkyusho and the Mylan (MYL) product, the last of which has since been discontinued.
Which darbepoetin alfa biosimilars are registered in the UAE?
None; Aranesp is registered.
What comparative evidence do regulators expect for darbepoetin alfa?
Analytical comparability including the glycan profile, pharmacokinetic and pharmacodynamic equivalence in healthy volunteers, and comparative efficacy in renal anaemia.
Work with EvySaif on darbepoetin alfa
Darbepoetin alfa 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 darbepoetin alfa, with the gaps ranked and a filing sequence recommended.
About the gap assessmentSources
S014CDSCO, permissions granted in Form 46 and 46A, to 2019 Primary (regulator)S020PMDA, list of approved biosimilar products in Japan (as of July 2026) 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)S018UAE Emirates Drug Establishment, registered medical product directory Primary (regulator)S009CDSCO and DBT, Guidelines on Similar Biologics 2016 Primary (regulator)S010CDSCO, Draft Guidelines on Similar Biologics 2025 Primary (regulator)
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