Agalsidase beta biosimilars
Enzyme replacement therapy for Fabry disease, with a single biosimilar in the world, approved in Japan in 2018.
About agalsidase beta
Recombinant human alpha-galactosidase A, a homodimeric glycoprotein of about 100 kDa produced in Chinese hamster ovary cells, with mannose-6-phosphate-bearing glycans that direct it to lysosomes.
Replaces the deficient lysosomal enzyme in Fabry disease, hydrolysing globotriaosylceramide accumulated in the endothelium, kidney, heart and nerves. Uptake into cells depends on the mannose-6-phosphate receptor, so the glycan profile determines efficacy.
Intravenous infusion every two weeks; plasma half-life about 45 to 100 minutes, with the clinical effect determined by tissue uptake rather than plasma exposure.
1 mg per kg every two weeks by intravenous infusion, from 5 mg and 35 mg lyophilised vials.
- Fabry disease (alpha-galactosidase A deficiency)
Most male patients develop IgG antibodies to agalsidase, which can reduce enzyme activity and cause infusion reactions. Comparative programmes are constrained by the rarity of the disease and rest on analytical similarity, particularly the mannose-6-phosphate glycan profile, pharmacokinetic comparison, and a small comparative study using plasma globotriaosylceramide or lyso-Gb3.
Fabrazyme was authorised in the EU on 3 August 2001 (EMEA/H/C/000370) and licensed by FDA on 24 April 2003 (BLA 103979). JCR Pharmaceuticals' agalsidase beta biosimilar, approved in Japan on 21 September 2018, remains the only biosimilar of an enzyme replacement therapy approved anywhere.
Sources: Purple Book (S016), EMA medicines data (S017), PMDA list (S020).
Agalsidase beta is in the Atlas as the one example of a biosimilar enzyme replacement therapy, and as a reminder that Japan has approved biosimilars no other regulator has. Ultra-rare disease, a glycan-dependent mechanism and a small comparative study make it a template for the lysosomal enzymes that may follow.
Sources: Fabrazyme 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 | Agalsidase Beta BS [JCR] | JCR Pharmaceuticals | Sep 2018 | not published | Approved | S020 |
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 PMDA's list and the UAE directory do not publish application numbers; Canadian dates are the first approval or market date recorded in the Drug Product Database.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 agalsidase beta 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 agalsidase beta programmes. Regulatory strategy consulting
Presentations and concentration
5 mg and 35 mg lyophilised vials for infusion.
| Product | FDA | EMA | PMDA | HC | CDSCO | EDE |
|---|---|---|---|---|---|---|
| Agalsidase Beta BS JCR | · | · | 5 mg and 35 mg vials | · | · | · |
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 |
|---|---|---|---|---|---|---|---|
| JCR Pharmaceuticals | Agalsidase Beta BS JCR | · | · | ✓ | · | · | · |
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
Is there an agalsidase beta biosimilar in the United States or the European Union?
No. The only biosimilar approved anywhere is JCR Pharmaceuticals' product in Japan, approved in September 2018.
Is there an agalsidase beta biosimilar in India?
No. Agalsidase beta does not appear in CDSCO's published r-DNA lists.
Which agalsidase beta biosimilars are registered in the UAE?
None; Fabrazyme is registered.
Why is this the only enzyme replacement biosimilar?
Enzyme replacement therapies depend on glycan-mediated uptake into cells, treat very rare diseases, and their reference products are protected by manufacturing know-how more than patents, so few developers have attempted them.
What comparative evidence did Japan accept for agalsidase beta?
Analytical comparability including the mannose-6-phosphate glycan profile, pharmacokinetic comparison, and a small clinical comparison in Fabry disease patients.
Could the Japanese product be approved elsewhere?
It would need a separate application in each market; no filing appears in EMA's list of applications under evaluation as of August 2026.
Work with EvySaif on agalsidase beta
Agalsidase beta 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 agalsidase beta, with the gaps ranked and a filing sequence recommended.
About the gap assessmentSources
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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