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The European Commission provided a positive opinion from the European Medicines Agency (EMA) Committee for Advanced Therapies, providing an Advanced Therapy Medicinal Product (ATMP) classification to OCU400 (Ocugen, Inc.). OCU400 is the first gene therapy from the biotechnology company to move forward into Phase 3 with a broad retinitis pigmentosa (RP) indication.

ATMP classification is given to medicines that allow for innovative opportunities for the treatment of disease, thus accelerating the regulatory review timeline of the new gene therapy. The classification will also allow for further collaboration between Ocugen and the EMA, with the EMA in place for scientific advice and protocol assistance as the company pushes for Marketing Authorisation Application (MAA) filing in 2026.

“Receiving ATMP classification is another significant milestone toward bringing OCU400 to the market in Europe,” said Shankar Musunuri, chairman, CEO and co-founder of Ocugen. “This designation makes it possible to stay on track with our clinical and commercial strategy and potentially provide this novel modifier gene therapy candidate to all RP patients in the United States and Europe by 2027.”

Besides the EMA, the FDA has also acknowledged that the Phase 3 trial of OCU400 can suffice for Biologics License Application (BLA) and MAA submissions. Ocugen, Inc. plans to file simultaneously in the US and Europe after completion of the trial.

Currently, the Phase 3 OCU400 trial is undergoing enrollment, and the study has a sample size of 150 participants. Patients 8 years old and older with early through late-stage advancement of RP are being recruited to take part in the study.

“We are encouraged by the EMA’s recognition of OCU400 as the Phase 3 liMeliGhT clinical trial advances,” Huma Qamar, chief medical officer at Ocugen, said. “I look forward to working collaboratively with the EMA to address the unmet medical need that remains for nearly 98% of the RP patient population.”

Ocugen Announces Positive Opinion of European Medicines Agency’s Committee for Advance Therapies for Advanced Therapy Medicinal Product Classification for Modifier Gene Therapy Candidate OCU400 for Retinitis Pigmentosa. News release. Ocugen. Published February 3, 2025. Accessed February 3, 2025. https://www.globenewswire.com/news-release/2025/02/03/3019337/0/en/Ocugen-Announces-Positive-Opinion-of-European-Medicines-Agency-s-Committee-for-Advanced-Therapies-for-Advanced-Therapy-Medicinal-Product-Classification-for-Modifier-Gene-Therapy-Ca.html

OCU400 is the first gene therapy from the biotechnology company to move forward into Phase 3 with a broad retinitis pigmentosa (RP) indication

Ocugen, Inc. receives European Medicines Agency ATMP designation for new gene therapy OCU400

On 13 January, Teva Pharmaceuticals International GmbH, a subsidiary of Teva Pharmaceutical Industries Ltd., announced it would partner with Klinge Biopharma GmbH and Formycon AG in commercialising FYB203, Formycon’s biosimilar candidate to aflibercept (Eylea, Regeneron Pharmaceuticals Inc.) in designated regions of Europe.

 On 5 February, Formycon announced that Klinge Biopharma had also concluded an exclusive license agreement with Lotus Pharmaceutical.

 This new agreement will enable commercialisation of the product throughout the Asia-Pacific region. Pending regulatory approval, the product will be marketed under the brand name AHZANTIVE.

Under these agreements, Teva will lead the commercialisation effort in designated regions of Europe, excluding Italy, and in Israel. Lotus Pharmaceutical will lead commercialisation in Indonesia, Malaysia, the Philippines, Singapore, Taiwan, Thailand and Vietnam, as well as within the Special Administrative Region Hong Kong.

Previously, Teva was established as the European commercialisation partner of FYB201, Formycon's biosimilar to ranibizumab (Lucentis). Nicola Mikulcik, hief business officer of Formycon, commented on the expansion of the partnership. “With Teva, we are gaining a strong and proven partner for FYB203 in the major parts of Europe and Israel. Teva is already marketing our FYB201 ranibizumab biosimilar (Ranivisio/Ongavia) in Europe and can synergistically leverage an existing commercial infrastructure and well-established distribution channels in the ophthalmology field,” she said in the press release.

 “We are pleased to build on this trusted and successful collaboration. Particularly noteworthy is Formycon’s first-time responsibility for managing the entire commercial supply chain of the finished product.”

Like its reference product, the biosimilar FYB203 is an anti-vascular endothelial growth factor (VEGF) agent used to treat retinal disease. Chief among those indications is neovascular age-related macular degeneration (AMD), also known as wet AMD.

In November 2024, the European Medicines Agency's Committee for Medicinal Products of Human Use issued a positive recommendation for marketing authorisation of FYB203, under the brand names AHZANTIVE/Baiama. The European Commission is expected to announce a response to the authorisation application in late January 2025.

In June 2024, the US Food and Drug Administration (FDA) approved the biosimilar FYB203, also known as aflibercept-mrbb. In a press release at that time, the company stated3 that FDA approval was rooted in the company's “comprehensive data package” that included “analytical, pre-clinical, clinical and manufacturing data.” The data showed that FYB203 demonstrated comparable efficacy, safety, pharmacokinetics and immunogenicity to the reference product in patients with neovascular AMD.

Teva Announces Collaboration to Commercialize Formycon’s Biosimilar Candidate to Eylea® (aflibercept) in major parts of Europe and in Israel. News release. Teva Pharmaceutical Industries Ltd. Published January 13, 2025. Accessed January 13, 2025. https://www.globenewswire.com/news-release/2025/01/13/3008103/0/en/Teva-Announces-Collaboration-to-Commercialize-Formycon-s-Biosimilar-Candidate-to-Eylea-aflibercept-in-major-parts-of-Europe-and-in-Israel.html

Lotus Pharmaceutical becomes strategic partner for the commercialization of Formycon’s Eylea® biosimilar FYB203/AHZANTIVE® in the Asia-Pacific Region. News release. Formycon AG. Published February 5, 2025. Accessed February 5, 2025.

Harp M. FDA approves Formycon’s biosimilar to Eylea, aflibercept-mrbb (Ahzantive). Ophthalmology Times. Published July 2, 2024. Accessed January 13, 2025. https://www.ophthalmologytimes.com/view/fda-approves-formycon-s-biosimilar-to-eylea-aflibercept-mrbb-ahzantive-

The commercialisation agreements for the biosimilar to aflibercept (Eylea) cover Israel, major parts of Europe and the Asia-Pacific Region

Teva partners with Klinge Biopharma, Lotus Pharmaceutical for commercialisation of Formycon’s FYB203 (biosimilar aflibercept)

Over the last 15 years, biosimilars have become a major feature of the health care landscape. Physicians in many disciplines, particularly oncology and immunology, have embraced biosimilars. However, access to educational resources on these powerful biologics can be inconsistent, and in turn, some ophthalmologists who could benefit from the adoption of biosimilars are left in the dark.

The real-world application of biosimilars was the focus of discussion for Martin Zinkernagel, MD, PhD, chair of the Department of Ophthalmology at the University Hospital of Bern, Switzerland, and Paolo Lanzetta, MD, professor of ophthalmology and chairman of the Department of Medicine-Ophthalmology at the University of Udine in Italy. In their discussion, the experts addressed several common questions, framed around the phase 3 clinical trial for biosimilar SB11 (BYOOVIZ) from Biogen. SB11 is approved in Europe and the United Kingdom. Like the reference product ranibizumab (Lucentis), SB11 is approved for the treatment of retinal disease including neovascular age-related macular degeneration (nAMD).

Addressing physicians’ levels of familiarity with biosimilars, Dr Lanzetta attributed much of the variation to regulatory discrepancies. “The uptake of biosimilars varies throughout Europe by country and by product,” he said. “Obviously, variation in the uptake of biosimilars [is] influenced by government involvement, reimbursement issues and tender procurement policies.” Recent survey data have revealed gaps in awareness across Europe and in the United States on the efficacy and safety of biosimilars for retinal diseases, Dr Lanzetta said, especially in terms of “real-world data.”

In a clinical application, Dr Lanzetta said, biosimilars may exhibit minor differences from the reference products, but they aren’t considered to have significant impact on the efficacy or safety profile. Typically, the biosimilar and reference medicine must have the same posology and route of administration, with few exceptions, he added.

Dr Lanzetta also said that in the last 10 years, the European Medicines Agency (EMA) has approved the highest number of biosimilars worldwide.

 “And this means, to us physicians, having both the possibility to have experience on their use in terms of safety and evaluating the efficacy after that,” he explained.

One common misconception about biosimilars is that these therapeutics are interchangeable with the idea of generic medicines. But there is a key indicator that biosimilars are unique: the cost. “While generic medicines are marketed at a significantly lower price than name brand ones, why do we not see the same level of cost savings with biosimilars?” Dr Zinkernagel asked.

Dr Lanzetta explained that biosimilars are developed via a rigorous, complex and highly regulated manufacturing process. “Generics are simple chemical medicines or agents, which is not the case for biosimilars and biologics,” he said. “Unlike generics, biologics, and therefore biosimilars as well, are very complex; they’re very difficult to copy. And the development processes are patented and proprietary to the originators.” The proprietary nature of biologic development, he added, is why biosimilars may have differences from their originators.

Prof Zinkernagel and Dr Lanzetta used data from the SB11 phase 3 trial to expand upon the capabilities of biosimilars. Prof Zinkernagel detailed the study: over 700 patients were included in the randomised, double-masked, parallel-group multicentre trial. Over 52 weeks, investigators evaluated the efficacy and the safety profile of this biosimilar SB11 in comparison with monthly ranibizumab for the treatment of nAMD.

“Patients with neovascular AMD were included, [with a] visual acuity range between 20/40 and 20/200,” Prof Zinkernagel said. “[Patients] were randomised in a 1:1 ratio to either have the originator or the biosimilar every 4 weeks from baseline up to week 48.”

Primary end-points were change from baseline in best corrected visual acuity at week 8 and change from baseline in central subfield thickness at week 4. The pre-specified secondary efficacy end-points included longer-term assessments of change from baseline in visual acuity, and the proportion of participants who lost fewer than 15 letters or who gained 15 or more letters in visual acuity from baseline at weeks 24 and 52.

“Other secondary end-points included, of course, change from baseline in central subfield thickness and central retinal lesion thickness at week 24, as well as change from baseline in choroidal neovascularisation [CNV] size and proportion of participants with active CNV leakage seen via OCT [optical coherence tomography] at week 24,” Prof Zinkernagel continued. Describing the results, he said, “When you look at the visual acuity improvements, it’s really equivalent. You have equivalence between the originator and the biosimilar, and the same holds true for a decrease in central retinal thickness. So the curves are basically the same, and also the secondary end-points.”

Prof Zinkernagel also spoke about the immunogenicity outcomes of the SB11 trial, as immunogenicity reactions have been a common problem in past assessments of anti–vascular endothelial growth factor (VEGF) agents. Along with detrimental effects to visual acuity, immunogenicity reactions can also lead to vasculitis and vitritis.

“Now, in this trial, the overall cumulative incidence of anti-drug antibodies, antibodies reacting against this specific drug up to week 52, was very low,” Prof Zinkernagel said. “For the SB11 biosimilar, it was 4.2%, and for the originator it was 5.5%. So very, very similar.”

He also noted that most antibodies were non-neutralising, which generally indicates a weak antibody response. “Furthermore, no statistical or clinically relevant differences in the incidence of anti-drug antibodies and neutralising antibodies were observed between treatment groups at any of the time points,” Prof Zinkernagel explained.

Dr Lanzetta highlighted the unique potentialities for anti-VEGF therapies as an area where physicians can consider treating patients with a biosimilar. “You can either switch a patient from the originator, obviously, or you can also consider treating with a biosimilar treatment-naive patients who may benefit…from being treated with that reference agent or originator agent,” he said. When to deploy a biosimilar will depend on many factors, including the locality where a patient is being treated. “Europe has different countries, different health care systems,” Dr Lanzetta said. “You may consider treating with the biosimilar patients who may not be strictly adherent to the cost of therapy and the frequency of treatment because of some cost issues.”

Just as education on biosimilars is vital to practitioners, awareness and education resources for patients are vital, too. “We spend a lot of time with our patients in letting them know that biologics did undergo a very rigorous approval process through studies, efficacy and safety studies,” Dr Lanzetta emphasised. This education is vital to getting patients on board with biosimilars, and it sparks enthusiasm about the potential benefits. “Once they do understand that, I think they will be very prone to receive a biosimilar; [it’s] in their interest and in the interest of the community, the whole community of patients, and in the interest of the health care system,” Dr Lanzetta said.

1. Biosimilars in the EU: information guide for healthcare professionals. European Medicines Agency. Updated December 2, 2019. Accessed October 3, 2023. 

https://www.ema.europa.eu/en/documents/leaflet/biosimilars-eu-information-guide-healthcare-professionals_en.pd

Editor’s note: A prior version of this article contained a misspelling of the product name BYOOVIZ. It has been corrected. We regret the error.

How biosimilars expand treatment options for patients with retinal disease

At the American Society of Cataract and Refractive Surgeons annual meeting, Sheng Lim, MD, FRCOphth discusses the benefit of endoscopic cyclophotocoagulation for patients with primary open angle glaucoma and cataracts in the CONCEPT study

At the American Society of Cataract and Refractive Surgeons (ASCRS) annual meeting in Los Angeles, California, the scientific programme went beyond refractive correction and cornea care. Gene and cell therapy, collaboration with retina specialists and pearls for glaucoma management were all part of the agenda as well.

Sheng Lim, MD, FRCOphth, is a professor of glaucoma studies at St. Thomas’ Hospital and King’s College London, both in the United Kingdom. At this year's meeting, he presented findings from a recent study, Comparing the Effectiveness of Phacoemulsification + Endoscopic Cyclophotocoagulation Laser and Phacoemulsification Alone for the Treatment of Primary Open Angle Glaucoma in Patients with Cataract (CONCEPT).

 editorial teams to illustrate why endoscopic cyclophotocoagulation (ECP) has major potential for patients with glaucoma. "We had over 160 patients in the study and randomisations 1 to 1, so it's interesting, the results we're getting so far, [after] 1 year," Prof. Lim said. "What the CONCEPT study has shown in 1 year is that we're seeing a median difference in IOP of 2 mm mercury, in support of use of ECP in primary open-angle glaucoma."

Prof. Lim also addressed a real-world postsurgical outcome which may differ from the clinical trial result: incidences of uveitis. "What we see in this study is that, during that follow up period, particularly in the first 2 months, you're seeing a higher incidence of anterior uveitis in the groups of patients who had ECP," he said. "Really, it's not surprising, because [patients who received ECP] were subjected to 

 the same post-op regime as a cataract surgery patient would have. But in real world, I think most people realise that if you combine cataract surgery with ECP, you have to increase the dosage and the length of steroid drop treatment for those groups of patients. So, I'm sure with those two adjustments, the incidence of significant anterior uveitis will be much reduced, if you do ECP with more steroid drops post operatively."

Endoscopic cyclophotocoagulation (ECP) has major potential for patients with glaucoma

Sheng Lim, MD, FRCOphth, brings data from the CONCEPT study to the ASCRS meeting

German researchers from the Department of Ophthalmology, Ludwig-Maximilians-Universität München University Hospital, Munich, recently reported on the “potential of artificial intelligence (AI)-driven biomarker segmentation as a precise and scalable tool for monitoring disease progression in treatment-resistant neovascular age-related macular degeneration (nAMD).”

They believe this potential will provide clinicians with valuable information about patient responses to treatment,

 according to the lead author Michael Hafner, MD.

Advancements in anti-vascular endothelial growth factor (VEGF) medications to treat AMD have resulted in significant visual improvements for patients. However, not all patients achieve optimal responses, according to the study authors. For patients who do not respond optimally and have persistent macular fluid despite monthly injections or the inability to extend treatment intervals beyond 4 to 6 weeks, the dual mechanism of action of faricimab (Vabysmo, Roche/Genentech) may offer advantages,

“The activity of macular neovascularisation in nAMD is commonly indicated by an increase in different optical coherence tomography (OCT) biomarkers such as mean central retinal thickness (CRT) (mean retinal thickness within the 1-mm ETDRS-circle centred on the fovea), and the presence of fibrovascular pigment epithelium detachment (fvPED), subretinal hyperreflective material (SHRM) and macular fluid, including intraretinal fluid (IRF) and subretinal fluid (SRF),” the authors indicated.

The phase 3 trials LUCERNE and TENAYA suggested that faricimab may allow for more efficient disease management by extending the interval between injections to up to 16 weeks after an initial loading phase of four monthly doses.

Dr Hafner and colleagues conducted a retrospective real-world study in which they analysed patients with treatment-resistant nAMD who had been switched to faricimab after having inadequate responses to ranibizumab (Lucentis, Genentech) or aflibercept (Eylea, Regeneron). The safety and efficacy of faricimab was assessed over a 9-month period.

To gauge the effect of faricimab, the investigators conducted automated segmentation of key OCT biomarkers, including fvPED, IRF, SRF, SHRM, choroidal volume and CRT using a deep learning algorithm based on a convolutional neural network.

They explained that to gain a deeper understanding of the mode of action of faricimab and therapeutic progression, investigators must look deeper than the CRT and best-corrected visual acuity (BCVA) and evaluate the biomarkers associated with nAMD.

A total of 46 eyes (41 patients) completed the 9-month follow-up evaluation.

The investigators found significantly reduced SRF, fvPED and choroidal volume from baseline to 3 months, and the reductions were sustained at 9 months. The CRT also decreased significantly from 342.7 (interquartile range [IQR] 117.1) µm at baseline to 296.6 (IQR: 84.3) µm at 3 months and 310.2 (IQR: 93.6) µm at 9 months.

Dr Hafner and colleagues commented that the deep learning model precisely quantified the biomarkers, enabling reliable tracking of disease progression.

The faricimab injection interval extended from 35 (IQR: 15) days at baseline to 56 (IQR: 20) days at 9 months, representing a 60% increase and reducing the treatment burden. The patients’ visual acuity remained stable throughout the study. Correlation analysis showed that higher baseline CRT and fvPED volumes were associated with greater BCVA improvements and longer treatment intervals.

In commenting on the results, the authors said, “Correlation analysis identified baseline biomarkers, specifically CRT, SRF, and fvPED, as potential predictors of extended treatment intervals, offering valuable insights for personalized therapy optimization. Patients with high baseline CRT and large fvPED volumes also exhibited greater improvements in BCVA, suggesting that specific subgroups may derive enhanced benefits from the dual inhibition of VEGF and angiopoietin-2 by faricimab.”

They believe that integrating AI-assisted OCT analysis into the clinical workflow will improve the precision and efficiency of disease monitoring, and advised that future research should focus on prospective, multicentre validation studies with longer follow-up durations to further assess long-term efficacy of faricimab and refine predictive models for personalised treatment strategies in nAMD.

Hafner M. Eckardt F, Siedlecki J, et al. Deep learning assisted analysis of biomarker changes in refractory neovascular AMD after switch to faricimab. 

https://doi.org/10.1186/s40942-025-00669-2

Mettu PS, Allingham MJ, Cousins SW. Incomplete response to anti-VEGF therapy in neovascular AMD: exploring disease mechanisms and therapeutic opportunities. 

Ozdemir S, Finkelstein E, Lee JJ, et al. Understanding patient preferences in anti-VEGF treatment options for age-related macular degeneration. 

Siedlecki J, Fischer C, Schworm B, et al. Impact of sub-retinal fluid on the long-term incidence of macular atrophy in neovascular age-related macular degeneration under treat & extend anti-vascular endothelial growth factor inhibitors. 

Schmidt-Erfurth U, Chong V, Loewenstein A, et al. Guidelines for the management of neovascular age-related macular degeneration by the European society of retina specialists (EURETINA). 

Heier JS, Khanani AM, Quezada Ruiz C, et al. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials. 

The phase 3 LUCERNE and TENAYA trials suggested that faricimab may allow clinicians to extend the interval between injections to up to 16 weeks after an initial loading phase

Artificial intelligence analyses biomarker changes in neovascular AMD treated with faricimab

Bayer announced the submission of an application to the European Medicines Agency (EMA) seeking to expand the indication for aflibercept 8 mg. This dosage of aflibercept (Eylea) will be assessed for treatment of macular oedema following retinal vein occlusion (RVO). Central, branch and hemiretinal RVO are included in this application, Bayer said in a press release. Aflibercept 8 mg is currently approved for the treatment of patients with neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO).

The submission is based on positive results from the phase 3 QUASAR study. In December 2024, Regeneron Pharmaceuticals announced that the trial met its primary endpoint.

 Aflibercept is being jointly developed by Bayer and Regeneron.

The QUASAR trial compared aflibercept 2 mg with aflibercept 8 mg in patients with RVO, and the primary endpoint was mean change in best corrected visual acuity (BCVA) through week 36. Patients receiving aflibercept 8mg were treated with an 8-week dosing regimen, following three or five initial monthly doses; patients receiving aflibercept 2 mg were treated every 4 weeks.

 indicated aflibercept 8 mg results were consistent across patients with branch retinal vein occlusions, and those patients with central retinal or hemiretinal vein occlusions. Of the patients treated with aflibercept 8 mg through 36 weeks, 88% of patients were able to sustain an 8-week dosing regimen following 3 initial monthly doses, and 93% of patients maintained an 8-week dosing regimen after completing 5 initial monthly doses.

Additionally, according to the press release from Bayer

 nearly 70% of those patients had a last assigned dosing interval of 12 weeks. Fluid reduction was similar between the patient groups who received aflibercept 8 mg and aflibercept 2 mg. Finally, Bayer reported, aflibercept 8 mg was well tolerated and its safety profile was consistent with previous trials.

Christine Roth, executive vice president of global product strategy and commercialisation and member of the pharmaceuticals leadership team at Bayer, commented on the submission.

 “Today’s submission is an important step towards improving patient care in retinal vein occlusion,” she said. “Once approved, aflibercept 8 mg expands durable treatment options alleviating the burden of frequent injections and clinic visits for patients living with retinal vein occlusion.”

In the United States, Regeneron maintains exclusive rights to aflibercept 2 mg (Eylea 2 mg) and aflibercept 8 mg (Eylea HD); outside the US, Bayer has licensed exclusive marketing rights. According to prior statements

 by Regeneron, the companies are also seeking approval from the US Food and Drug Administration for the third indication of aflibercept 8 mg.

Bayer files for approval of aflibercept 8 mg for treatment of retinal vein occlusion in EU. Press release. Bayer. Published April 8, 2025. Accessed April 9, 2025. 

https://firstwordpharma.com/story/5948151

Harp M D. Regeneron announces aflibercept 8mg injection meets primary endpoint in phase 3 QUASAR trial in patients with retinal vein occlusion. 

Published December 17, 2024. Accessed April 9, 2025. 

https://www.ophthalmologytimes.com/view/regeneron-announces-aflibercept-8mg-injection-meets-primary-endpoint-in-phase-3-quasar-trial-in-patients-with-retinal-vein-occlusion

Harp M D. Regeneron reveals positive results from multiple trials evaluating Eylea HD (aflibercept) injection 8 mg. 

Published February 10, 2025. Accessed April 9, 2025.

In the European Union and the United Kingdom, aflibercept 8 mg (Eylea HD in the US) is currently approved for neovascular age-related macular degeneration and diabetic macular oedema 

Dr Giacomo Savini

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