New ranibizumab biosimilar enters the market

• Ranibizumab story shows how a transformative biologic can create a therapeutic market and then become the reference point for a highly competitive biosimilar industry.
• This biologic drug is the gold standard in the treatment of retinal diseases. Clinical trials have repeatedly demonstrated its effectiveness. It has transformed the clinical landscape of a wide range of devastating ophthalmological conditions.
• The primary advantage of ranibizumab biosimilars is price. The introduction of biosimilars to the market has led to price reductions for anti-VEGF therapies by up to 40%. This significantly improves patient compliance and treatment initiation.

Ranibizumab transformed the management of retinal vascular diseases by demonstrating that an intravitreally administered biologic could do more than delay blindness. It could improve vision. Today, Lucentis and its biosimilars are used, with some jurisdictional differences in labelling, for:

• Neovascular age-related macular degeneration (nAMD)
• Diabetic macular oedema (DME)
• Diabetic retinopathy (DR)
• Choroidal neovascularization (CNV)
• Macular oedema following retinal vein occlusion (RVO)
• Myopic choroidal neovascularisation (mCNV)
• Retinal ischemia

How does ranibizumab work?

Ranibizumab contains a recombinant, humanised and affinity-matured IgG1 kappa antigen-binding fragment, or Fab. The approximately 48-kDa molecule has no Fc region and is produced in an Escherichia coli expression system. Its smaller Fab-only structure was developed specifically for intraocular administration and supports penetration through retinal tissue while limiting prolonged systemic exposure.

The molecule was created through affinity maturation of an earlier humanised anti-VEGF antibody fragment. Complementarity-determining-region variants were generated and selected using monovalent phage display to improve affinity for vascular endothelial growth factor A (VEGF-A). This engineering history is important for biosimilar developers. The reference product is not merely a fragment cleaved from bevacizumab. It has its own optimised sequence, manufacturing process, quality profile and biological activity.

Ranibizumab binds active VEGF-A isoforms, including VEGF110, VEGF121 and VEGF165. By preventing VEGF-A from activating VEGFR-1 and VEGFR-2 on endothelial cells, biologic drug inhibits endothelial-cell proliferation, pathological angiogenesis and vascular permeability.^1,2

History of the development and approval of ranibizumab

Before the advent of anti-VEGF therapies like ranibizumab, physicians had limited tools for treating the retinal diseases that would later become ranibizumab indications. The treatment of serious eye diseases was limited to laser photocoagulation and verteporfin photodynamic therapy (PDT). These treatments were often more effective at slowing vision loss than regaining it, and retinal diseases remained the leading cause of blindness in adults over 60.³

Lucentis – the first effective drug to improve vision

The identification of VEGF-A as a central mediator of angiogenesis and vascular permeability created a drug-development opportunity. Genentech had already developed the full-length anti-VEGF antibody, bevacizumab. However for ophthalmology the company developed a separate, affinity-matured Fab molecule. It was optimised for intraocular use. Early studies established acceptable ocular safety, biological activity and dosing feasibility before the programme moved into large, masked clinical trials.

The decisive registration programme was built around two complementary phase III trials. MARINA enrolled patients with minimally classic or occult choroidal neovascularisation and compared monthly Lucentis with sham injections. ANCHOR enrolled patients with predominantly classic lesions and compared Lucentis against active treatment with Visudyne. In both populations, Lucentis not only prevented clinically significant vision loss but produced average improvements in visual acuity.

The FDA approved Lucentis for neovascular age-related macular degeneration on June 30, 2006. European patients gained access shortly after, with EMA marketing authorisation granted on 22 January 2007. The market impact extended beyond one product. Lucentis validated repeated intravitreal biologic administration, established anti-VEGF treatment as the standard of care and created a large physician-administered ophthalmic-biologics category. It also changed patient expectations.⁴

Lucentis provides new hope for patients with wet AMD because it is the first therapy to provide a benefit in vision for a significant number of patients. We are proud that the seminal work in angiogenesis conducted at Genentech, years of clinical study, and the dedication and commitment of thousands of patients and retina specialists have all contributed to this important FDA approval.

Over the following decade, Lucentis became a blockbuster biologic. This drug expanding its indications to RVO (2010), DME (2012), and mCNV (2017), with global sales reaching approximately $3.6 billion in 2015.⁵

The era of universal access to ranibizumab

Patents for the innovator molecule expired in June 2020 in the US and July 2022 in the EU. Their expiry triggered a wave of development programmes, regulatory submissions and regional commercial partnerships.

The first ranibizumab biosimilar market entry came earlier in India. Razumab, was approved in India in 2015, providing a version at nearly half the price of the innovator.⁶

The first wave of highly regulated approvals followed in 2021. Byooviz became the first ranibizumab biosimilar approved by both the FDA and EMA. In its phase III study, 705 patients with treatment-naïve nAMD received Byooviz or Lucentis every four weeks. Differences in visual acuity and central retinal thickness remained within predefined equivalence margins, with comparable safety through one year.⁷

FYB201 reached different markets as Cimerli, Ranivisio and Ongavia. The COLUMBUS-AMD study randomised 477 patients to FYB201 or Lucentis. Mean best-corrected visual-acuity gains were 5.1 and 5.6 letters, respectively, and the confidence interval remained within the predefined equivalence margin. That’s how Cimerli subsequently became the first FDA-designated interchangeable ranibizumab biosimilar for all Lucentis indications.⁸

Ximluci followed a similar model. Its XPLORE study enrolled 582 patients with nAMD and compared monthly Ximluci with Lucentis for 52 weeks. The study met the US and European equivalence criteria for change in visual acuity and found no clinically meaningful differences in anatomical, safety or immunogenicity outcomes.⁹

How competitors accelerated biosimilar approval?

The ranibizumab programmes illustrate the defining difference between innovator and biosimilar development. A biosimilar sponsor does not repeat the entire process used to establish that VEGF-A inhibition treats retinal disease. The objective is to demonstrate, through the totality of evidence, that the candidate is highly similar to Lucentis and has no clinically meaningful differences in safety, purity or potency.

Development normally begins with extensive characterisation of multiple Lucentis lots. The target profile includes:

• Amino-acid sequence
• Disulphide structure
• Higher-order conformation
• Product-related variants
• Aggregation
• Charge heterogeneity
• VEGF-A binding
• Inhibition of VEGF receptor signalling
• Protein concentration
• Formulation
• Stability

Developers avoid the glycan-comparability challenge associated with CHO-derived full-length antibodies, but they must control folding, disulphide pairing, fragmentation, oxidation, aggregation and host-cell impurities.

Analytical similarity forms the foundation of the programme. Its conclusions determine the extent of subsequent non-clinical and clinical work. Regulatory authorities require a full quality dossier and comparative evidence rather than a lower manufacturing standard.

Clinical development has generally used treatment-naïve nAMD as a sensitive population. Visual acuity measured in ETDRS letters and optical-coherence-tomography measurements provide responsive, well-established endpoints. Clinical trials used narrow equivalence margins: ±3 letters for Byooviz, ±3.5 letters for FYB201 and approximately ±3.5 letters for Ximluci. This design is intended to detect clinically relevant differences, not to prove superiority.¹⁰

Once biosimilarity is demonstrated, regulators may extrapolate approval to additional Lucentis indications. Extrapolation is based on the total comparability package, common mechanism of action, receptor biology, pharmacology, safety and immunogenicity.

The regulatory environment is also moving toward more tailored biosimilar development. EMA’s 2026 reflection work considers circumstances in which strong structural and functional comparability, together with comparative pharmacokinetic data, could reduce or remove the need for a conventional comparative efficacy study. This could shorten future development, but it increases rather than decreases the importance of analytical science and process understanding.

More biosimilars entering the market

The second wave is broader than a simple repetition of Byooviz and Cimerli. It combines new manufacturers, additional formulations, regional licensing partnerships and renewed commercialisation of previously approved products.

On February 10, 2026, Ranluspec is authorised by the EMA. On June 2, 2026, the FDA approved Ranluspec as biosimilar to and interchangeable with US-licensed Lucentis. The approval covers 0.3-mg and 0.5-mg strengths in both single-dose glass vials and prefilled syringes. The dual-presentation approval is commercially important because it allows the supplier to address clinics that prefer ready-to-inject syringes. Interchangeability may permit pharmacy-level substitution without prescriber intervention, depending on state law.¹¹

Following a positive CHMP opinion on April 23, the European Commission granted Rexatilux marketing authorisation on June 19, 2026. Its label covers all typical indications. EMA concluded that its quality, safety and efficacy were comparable with Lucentis and that the complete originator efficacy programme did not need to be repeated.

Susvimo belongs in the competitive discussion but not in a list of biosimilars. EMA’s CHMP recommended Susvimo for adults with stable nAMD who had responded to previous anti-VEGF injections. Susvimo addresses a different component of value: treatment burden rather than acquisition price alone. The customised formulation is delivered continuously through the Contivue refillable implant, which is refilled every six months.¹²

Recent systematic meta-analysis covering 24 studies found no clinically meaningful difference between Lucentis and ranibizumab biosimilars in visual-acuity change, central macular thickness or adverse-event rates.¹³

Ranibizumab market share in 2026

Published literature commonly reports ranibizumab biosimilar discounts of approximately 20–30%, while some analyses cite reductions of 35–50% compared with the originator. The growing number of approved products does not guarantee immediate availability in every country. Reimbursement, tenders, national pricing, distribution and commercial-partner decisions determine actual market access.

The most recent publicly accessible US report, released in July 2026, places the combined ranibizumab-biosimilar share at 6% of US ranibizumab volume as of the first quarter of 2026, up four percentage points from the preceding quarter. This implies that Lucentis retained approximately 94% of the US market. The earlier US experience provides a warning against treating the lowest price as the only success metric. In the third quarter of 2024, commercial data placed Cimerli at approximately 49% of ranibizumab volume, ahead of Lucentis at 43% and Byooviz at 8%. Rapid average-sales-price erosion was followed by a pause in Cimerli supply, and its share subsequently fell to effectively zero. The episode demonstrates that aggressive contracting can generate fast uptake while undermining the economics needed to maintain production, inventory and commercial support.

The sharp reversal from majority biosimilar penetration in 2024 to only 6% in early 2026 is one of the most important lessons in the ranibizumab story. Biosimilar share is not automatically permanent. Supply continuity, commercial ownership and operational support can be as important as regulatory approval.

FAQ

Prepared by:

Jakub Knurek

Marketing Specialist

j.knurek@mabion.eu

Jakub Knurek

Marketing Specialist

Jakub Knurek is a marketing and business development expert specializing in CDMO operations with scientific and biopharmaceutical background. During the COVID-19 pandemic, he contributed to the development of the Novavax protein vaccine. As a side project, he runs his own pharma company.

As the author of numerous articles, he is recognized as an important voice of the younger generation of scientists. He is a member of Mabion’s representation at industry trade shows, including Central European BioForum 2026, Eurobiotech Congress 2026, BIO International Convention 2025 in Boston, 2nd Global Biologics India 2025 in Hydrabad, CPHI 2024 in Milan, CPHI 2023 in Barcelona, Life Sciences Baltics 2023 in Vilnius.

He actively participates in academic, business and industry discussions, such as the “Building the Future Pharma Workforce” panel at CPHI Milan 2024 or “Biotech in Translation: How to Tell the Story of Innovation” at Central European BioForum 2026.

Sources and further reading

1. Triantafylla M, Massa HF, Dardabounis D, Gatzioufas Z, Kozobolis V, Ioannakis K, Perente I, Panos GD. Ranibizumab for the treatment of degenerative ocular conditions. Clin Ophthalmol. 2014; 8: 1187-1198.
2. Ranjbar M, Brinkmann MP, Tura A, Rudolf M, Miura Y, Grisanti S. Ranibizumab interacts with the VEGF-A/VEGFR-2 signaling pathway in human RPE cells at different levels. Cytokine. 2016; 83: 210-216.
3. Mohammed AW, Al-Shaikhli MS, Suhail RI, Yahya AA, Al-hussaniy HA, Al-Tameemi ZS, Saleem ZM, Mahdi F. Targeting VEGF: a review of ranibizumab in retinal disorders. Pharmacia. 2025; 72: 1-10.
4. Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006; 355(14): 1419-1431.
5. Han-na P. BIOCND to start clinical trials of Lucentis’ biosimilar. The Korea Herald. 2016.
6. Sharma A, Kumar N, Parachuri N, Bandello F, Kuppermann BD, Loewenstein A. Ranibizumab Biosimilar (Razumab) vs Innovator Ranibizumab (Lucentis) in neovascular age-related macular degeneration (n-AMD)- efficacy and safety (BIRA study). Eye (Lond). 2022; 36(5): 1106-1107.
7. Bressler NM, Kim T, Oh I, Russo P, Kim MY, Woo SJ. Immunogenicity With Ranibizumab Biosimilar SB11 (Byooviz) and Reference Product Lucentis and Association With Efficacy, Safety, and Pharmacokinetics: A Post Hoc Analysis of a Phase 3 Randomized Clinical Trial. JAMA Ophthalmol. 2023; 141(2): 117-127.
8. Holz FG, Oleksy P, Ricci F, Kaiser PK, Kiefer J, Schmitz-Valckenberg S; COLUMBUS-AMD Study Group. Efficacy and Safety of Biosimilar FYB201 Compared with Ranibizumab in Neovascular Age-Related Macular Degeneration. Ophthalmology. 2022; 129(1): 54-63.
9. Björnestedt R, Waters S, Paišytė A, Furlan F, Wanner C. Evaluation of XSB-001 (Ranibizumab Biosimilar) Physicochemical and Biological Stability in Prepared Syringes for Intravitreal Injection. Adv Ther. 2025; 42(9): 4597-4610.
10. Sharma A, Loewenstein A, Parachuri N, Kumar N, Kuppermann BD. Biosimilar to Biosimilar Anti-VEGF Switching for Retinal Diseases. J Vitreoretin Dis. 2023; 7(6): 474-476.
11. Karkaria C, Gambuzza L. FDA approves ranibizumab-hkdz as first interchangeable biosimilar ranibizumab available in both vials and prefilled syringes. Ophthalmology Times. 2026.
12. Harp MD. CHMP recommends approval of Roche’s ranibizumab injection, 100 mg/mL (Susvimo), for treatment of nAMD. Ophthalmology Times. 2026.
13. Alamoudi A, Alnabihi A, Almufarriji N, AlQahtani AS. Efficacy and safety of ranibizumab biosimilars for neovascular age-related macular degeneration: A comprehensive systematic review and meta-analysis. AJO Int. 2026; 3(2): 100255.