Natalizumab biosimilars
Anti-integrin antibody for relapsing multiple sclerosis and Crohn's disease, with a single biosimilar, Tyruko, approved in the US and EU in 2023.
About natalizumab
Humanised IgG4 kappa monoclonal antibody of about 149 kDa, produced in a murine myeloma cell line, directed against the alpha-4 subunit of the alpha-4 beta-1 and alpha-4 beta-7 integrins.
Blocks the adhesion of alpha-4 integrin on lymphocytes to VCAM-1 on vascular endothelium and MAdCAM-1 in the gut, preventing leukocyte migration across the blood-brain barrier into the central nervous system and into inflamed intestine. The same mechanism carries the risk of progressive multifocal leukoencephalopathy, which shapes its use.
Intravenous infusion; half-life about 11 days, with dosing every four weeks giving near-complete alpha-4 integrin saturation. A subcutaneous 150 mg presentation of the reference product exists in some markets.
300 mg by intravenous infusion every four weeks, from 300 mg/15 mL (20 mg/mL) vials, within a risk-management programme that includes JC virus antibody testing.
- Relapsing forms of multiple sclerosis
- Crohn's disease (United States)
Persistent anti-natalizumab antibodies develop in about 6% of patients and are associated with loss of efficacy and infusion reactions, so comparative immunogenicity is a central part of the programme. Comparative programmes use analytical similarity, a pharmacokinetic and pharmacodynamic study using alpha-4 integrin saturation, and a comparative efficacy study in relapsing multiple sclerosis with new active lesions on MRI at 24 weeks as the primary endpoint.
Tysabri was licensed by FDA on 23 November 2004 (BLA 125104), withdrawn within months after cases of progressive multifocal leukoencephalopathy, and reintroduced in 2006 under a risk-management programme; it was authorised in the EU on 27 June 2006 (EMEA/H/C/000603). Polpharma's PB006, commercialised by Sandoz as Tyruko, was approved by FDA in August 2023 and authorised in the EU in September 2023 as the first, and so far only, natalizumab biosimilar.
Sources: Purple Book (S016), EMA medicines data (S017), CDSCO import list (S013).
Natalizumab shows a biosimilar entering a market defined by a safety programme rather than by price alone: the biosimilar must fit the same JC virus testing and PML monitoring as the reference, and the launch depended on a companion assay. One developer has done it. There is no Indian or Gulf biosimilar activity; India's only entry is Eisai's import permission for the reference product.
Sources: Tysabri 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 |
|---|---|---|---|---|---|---|---|
| FDA | Tyruko | Sandoz Inc. | Aug 2023 | 761322 | Biosimilar | Approved | S001, S016 |
| EMA | Tyruko | Sandoz GmbH | Sep 2023 | EMEA/H/C/005752 | Approved | S017 |
CDSCO lists permissions by firm and INN, not brand. The UAE directory does not publish registration numbers.
Regulatory pathway by market
Requirements for a natalizumab biosimilar under the guidance in force in September 2026.
| FDA, United States | EMA, European Union | 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 | 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 | 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/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 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 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).
EvySaif prepares the comparative evidence plan and the regional dossier strategy for natalizumab programmes. Regulatory strategy consulting
Presentations and concentration
A single biosimilar presentation, 300 mg in 15 mL (20 mg/mL) concentrate for infusion. The 150 mg subcutaneous syringe exists only for the reference product.
| Product | FDA | EMA | CDSCO | EDE |
|---|---|---|---|---|
| Tyruko PB006 | 300 mg/15 mL vial | see SmPC | · | · |
Sources: Purple Book (S016), 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 | CDSCO | EDE |
|---|---|---|---|---|---|
| Polpharma Biologics | Tyruko | ✓ | ✓ | · | · |
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
Questions
How many natalizumab biosimilars has FDA approved?
One: Tyruko from Sandoz, approved on 24 August 2023. It is not designated interchangeable.
Which natalizumab biosimilars are authorised in the European Union?
One: Tyruko, authorised on 22 September 2023.
Is there a natalizumab biosimilar approved in India?
No. The only natalizumab entry in CDSCO's published lists is Eisai's import permission for the reference product, granted in March 2018.
Which natalizumab biosimilars are registered in the UAE?
None; Tysabri infusion and subcutaneous syringe are registered.
Does the biosimilar carry the same PML risk programme?
Yes. Tyruko is prescribed under the same JC virus antibody testing and monitoring requirements as Tysabri in both the US and the EU.
Which comparative efficacy study do regulators accept for natalizumab?
A study in relapsing multiple sclerosis with the cumulative number of new active lesions on MRI at 24 weeks as the primary endpoint, supported by pharmacokinetic and pharmacodynamic equivalence and comparative immunogenicity.
Work with EvySaif on natalizumab
Natalizumab 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 natalizumab, 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)S018UAE Emirates Drug Establishment, registered medical product directory Primary (regulator)S013CDSCO, import and market permissions till 2019 (r-DNA) 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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