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• Approval is based on data from two Phase III studies in branch and central retinal vein occlusion (RVO) showing early and sustained vision improvements non-inferior to aflibercept, and robust retinal drying with Vabysmo
• Additional submitted data shows that up to 60% of people receiving Vabysmo were able to extend treatment intervals to three or four months
• Vabysmo is already approved in several countries, including the US and Japan, for RVO and in nearly 100 countries for people with nAMD and DME
  

Basel, 30 July 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the European Commission (EC) has approved Vabysmo® (faricimab) for the treatment of visual impairment due to macular edema secondary to retinal vein occlusion (RVO, branch RVO or central RVO). RVO is the third indication for Vabysmo in the European Union, in addition to neovascular or ‘wet’ age-related macular degeneration (nAMD) and diabetic macular edema (DME).¹ Together, the three retinal conditions affect close to 80 million people worldwide and are among the leading causes of vision loss.^2-5

“Vabysmo is a new treatment option for people with retinal vein occlusion in Europe that can help preserve and improve vision, with the added benefit of retinal drying,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “The efficacy and safety of Vabysmo has been well established in global clinical trials and is reinforced by a growing breadth of real-world evidence, with hundreds of thousands of people treated worldwide.”

The approval is based on positive results from two global Phase III BALATON and COMINO studies, evaluating Vabysmo in more than 1,200 people with macular edema due to branch and central retinal vein occlusion (BRVO and CRVO).^6,7

“People with retinal vein occlusion have limited treatment options which require regular clinic visits,” said Prof. Frank Holz, chairman and professor, Department of Ophthalmology, University of Bonn, Germany. “This approval could have a significant impact for people who have retinal vein occlusion and their caregivers, who together have to navigate the devastating impact of their disease on their ability to drive, read, socialise, travel and pursue hobbies.”

Results demonstrated that monthly treatment with Vabysmo provided early and sustained improvement in vision in people with BRVO and CRVO, meeting the primary endpoint of non-inferior visual acuity gains at 24 weeks compared to aflibercept. This was further supported by data showing Vabysmo achieved rapid and robust drying of retinal fluid.⁸ Retinal drying is an important clinical measure as swelling from excess fluid in the back of the eye has been associated with distorted and blurred vision.⁹

Additional longer-term data up to 72-weeks showed that nearly 60% of people receiving Vabysmo in BALATON and nearly 48% of people in COMINO were able to extend their treatment intervals to three or four months apart.⁸ Current available treatments for RVO are typically given every one to two months.^10,11

In both studies, Vabysmo was well tolerated, and the safety profile was consistent with previous studies.

Vabysmo is the first and only bispecific antibody approved for the eye, uniquely engineered to target and inhibit two signalling pathways, which are linked to a number of vision-threatening retinal conditions, by neutralising angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A) to restore vascular stability.^12-15

Vabysmo was first approved for RVO by the United States (US) Food and Drug Administration in October 2023, and by the Japan Ministry of Health, Labour and Welfare in March 2024.^12,16 To date, Vabysmo is available in nearly 100 countries for people with nAMD and DME, with more than four million doses distributed globally.^{1,12,13,16-18}

About retinal vein occlusion (RVO)
RVO is the second most common cause of vision loss due to retinal vascular diseases. It affects an estimated 28 million adults globally, mainly those aged 60 or older, and can lead to severe and sudden vision loss.^5,19 The level of angiopoietin-2 (Ang-2) is elevated in RVO and it is thought that increased Ang-2 expression drives disease progression, alongside vascular endothelial growth factors (VEGF).^20,21 RVO typically results in sudden, painless vision loss in the affected eye because the vein blockage restricts normal blood flow in the affected retina, resulting in ischemia, bleeding, fluid leakage and retinal swelling called macular edema.^19,22,23 Currently, macular edema due to RVO is typically treated with repeated intravitreal injections of anti-vascular endothelial growth factor therapies.²² There are two main types of RVO: branch retinal vein occlusion, which affects more than 23 million people globally and occurs when one of the four smaller ‘branches’ of the main central retinal vein becomes blocked; and central retinal vein occlusion, which is less common, affecting more than four million people worldwide, and occurs when the eye’s central retinal vein becomes blocked.^5,23

About the BALATON and COMINO studies^6,7
BALATON (NCT04740905) and COMINO (NCT04740931) were two randomised, multicentre, global Phase III studies evaluating the efficacy and safety of Vabysmo®️ (faricimab) compared to aflibercept. For the first 20 weeks, patients were randomised 1:1 to receive six monthly injections of either Vabysmo (6.0 mg) or aflibercept (2.0 mg). From weeks 24-72, all patients received Vabysmo (6.0 mg) up to every four months using a treat-and-extend dosing regimen.

The BALATON study was conducted in 553 people with branch retinal vein occlusion. The COMINO study was conducted in 729 people with central retinal or hemiretinal vein occlusion.

The primary endpoint of each study was the change in best-corrected visual acuity from baseline at 24 weeks. Secondary endpoints included change in central subfield thickness and drying of retinal fluid from baseline over time up to week 24.

About the Vabysmo® (faricimab) clinical development programme
Roche has a robust Phase III clinical development programme for Vabysmo. The programme includes AVONELLE-X (NCT04777201), an extension study of TENAYA (NCT03823287) and LUCERNE (NCT03823300), evaluating the long-term safety and tolerability of Vabysmo in neovascular or ‘wet’ age-related macular degeneration (nAMD), and RHONE-X (NCT04432831), an extension study of YOSEMITE (NCT03622580) and RHINE (NCT03622593) evaluating the long-term safety and tolerability of Vabysmo in diabetic macular edema (DME).^24,25 Roche has also initiated several Phase IV studies, including the ELEVATUM (NCT05224102) study of Vabysmo in underrepresented patient populations with DME, the SALWEEN study of Vabysmo in a subpopulation of nAMD highly prevalent in Asia, and the POYANG (NCT06176352) study of Vabysmo in adult treatment-naive patients with choroidal neovascularisation secondary to pathologic myopia.^26-28 Roche has also initiated the VOYAGER (NCT05476926) study, a global real-world data collection platform, and supports several other independent studies to further understand retinal conditions with a high unmet need.²⁹

About Vabysmo® (faricimab)
Vabysmo is the first bispecific antibody approved for the eye.^12-14 It targets and inhibits two signalling pathways linked to a number of vision-threatening retinal conditions by neutralising angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). Ang-2 and VEGF-A contribute to vision loss by destabilising blood vessels, causing new leaky blood vessels to form and increasing inflammation. By blocking pathways involving Ang-2 and VEGF-A, Vabysmo is designed to stabilise blood vessels.^14,15 Vabysmo is approved in nearly 100 countries, including the United States (US), Japan, the United Kingdom and the European Union for people living with neovascular or ‘wet’ age-related macular degeneration and diabetic macular edema and in several countries, including the US and Japan, for retinal vein occlusion. Review by other regulatory authorities is ongoing. ^{1,12,13,16-18} 

About Roche in ophthalmology
Roche is focused on saving people’s eyesight from the leading causes of vision loss through pioneering therapies. Through our innovation in the scientific discovery of new potential drug targets, personalised healthcare, molecular engineering, biomarkers and continuous drug delivery, we strive to design the right therapies for the right patients.

We have the broadest retina pipeline in ophthalmology, which is led by science and informed by insights from people with eye diseases. Our pipeline includes innovative treatments across different modalities such as antibodies, gene and cell therapies targeting multiple vision-threatening conditions, including retinal vascular and diabetic eye diseases, geographic atrophy and autoimmune conditions, such as thyroid eye disease and uveitic macular edema.

Applying our extensive experience, we have already brought breakthrough ophthalmic treatments to people living with vision loss. Susvimo® (previously called Port Delivery System with ranibizumab) 100 mg/mL for intravitreal use via ocular implant is the first United States (US) Food and Drug Administration-approved refillable eye implant for neovascular or ‘wet’ age-related macular degeneration (nAMD) that continuously delivers a customised formulation of ranibizumab over a period of months.^30,31 Vabysmo® (faricimab) is the first bispecific antibody approved for the eye, which targets and inhibits two signalling pathways linked to a number of vision-threatening retinal conditions by neutralising angiopoietin-2 and vascular endothelial growth factor-A.^12-15 Vabysmo is approved around the world for people living with nAMD and diabetic macular edema, and in several countries, including the US and Japan, for macular edema following retinal vein occlusion.^{1,12,13,16-18} Lucentis® (ranibizumab injection)* was the first treatment approved to improve vision in people with certain retinal conditions.¹¹

About Roche
Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice.

In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the fifteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work.

Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan.

For more information, please visit www.roche.com.

*Lucentis® (ranibizumab injection) was developed by Genentech, a member of the Roche Group. Genentech retains commercial rights in the United States and Novartis has exclusive commercial rights for the rest of the world.

All trademarks used or mentioned in this release are protected by law.

References
[1] European Medicines Agency. Summary of product characteristics, Vabysmo. 2022. [Internet; cited July 2024]. Available from: https://www.ema.europa.eu/en/documents/product-information/vabysmo-epar-product-information_en.pdf.
[2] Bright Focus Foundation. Age-related macular degeneration: facts & figures. 2023. [Internet; cited July 2024]. Available from: https://www.brightfocus.org/macular/article/age-related-macular-facts-figures.
[3] Im JHB, et al. Prevalence of diabetic macular edema (DME) based on optical coherence tomography in people with diabetes: a systematic review and meta-analysis. Surv Ophthalmol. 2022 Jul-Aug;67(4):1244-1251.
[4] The Lancet. Diabetes: a defining disease of the 21st century. Lancet. 2023 Jun 24;401(10394):2087.
[5] Song P, et al. Global epidemiology of retinal vein occlusion (RVO): a systematic review and meta-analysis of prevalence, incidence, and risk factors. J Glob Health. 2019 Jun;9(1):010427.
[6] Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab in participants with macular edema secondary to branch RVO (BALATON) [Internet; cited July 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT04740905.
[7] Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab in participants with macular edema secondary to central retinal or hemi RVO (COMINO) [Internet; cited July 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT04740931.
[8] Ghanchi, et al. Efficacy, safety, and durability of faricimab in macular edema due to RVO: 72-week results from the Phase III BALATON and COMINO trials. Poster presented at: ARVO Annual Meeting, May, 5-9 2024, Seattle WA, US. Poster #A0388.
[9] United States (US) National Institutes of Health - National Eye Institute. Macular edema. 2023. [Internet; cited July 2024]. Available from: https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/macular-edema.
[10] US Food and Drug Administration (FDA). Highlights of prescribing information, aflibercept 2 mg. 2022. [Internet; cited July 2024]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125387s076lbl.pdf.
[11] US FDA. Highlights of prescribing information, Lucentis. 2014. [Internet; cited July 2024]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125156s0069s0076lbl.pdf.
[12] US FDA. Highlights of prescribing information, Vabysmo. 2023 [Internet; cited July 2024]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761235s003lbl.pdf.
[13] Medicines and Healthcare products Regulatory Agency approves faricimab through international work-sharing initiative. [Internet; cited July 2024]. Available from: https://www.gov.uk/government/news/mhra-approves-faricimab-through-international-work-sharing-initiative.
[14] Heier JS, et al. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular macular degeneration (nAMD) (TENAYA and LUCERNE): two randomised, double-masked, Phase III, non-inferiority trials. The Lancet. 2022;399:729-40.
[15] Wykoff C, et al. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with DME (YOSEMITE and RHINE): two randomised, double-masked, Phase III trials. The Lancet. 2022;399:741-755.
[16] Chugai obtains regulatory approval for Vabysmo, the only bispecific antibody in the ophthalmology field, for additional indication of macular edema associated with RVO. [Internet; cited July 2024]. Available from: https://www.chugai-pharm.co.jp/english/news/detail/20240326160000_1054.html.
[17] Chugai obtains regulatory approval for Vabysmo, the first bispecific antibody in ophthalmology, for nAMD and DME. [Internet; cited July 2024]. Available from: https://www.chugai-pharm.co.jp/english/news/detail/20220328160002_909.html.
[18] Roche data on file.
[19] Moorfields Eye Hospital, United Kingdom National Health Service Foundation Trust. RVO. [Internet; cited July 2024]. Available from: https://www.moorfields.nhs.uk/condition/retinal-vein-occlusion.
[20] Joussen et al. Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data. Eye. 2021;35:1305-1316.
[21] Regula JT, et al. Targeting key angiogenic pathways with a bispecific CrossMab optimised for neovascular eye diseases. EMBO Molecular Medicine. 2016;8:1265–88.
[22] Schmidt-Erfurth U, et al. Guidelines for the management of RVO by the European Society of Retina Specialists (EURETINA). Ophthalmologica. 2019;242:123-162.
[23] Campochiaro P. Molecular pathogenesis of retinal and choroidal vascular diseases. Prog Retin Eye Res. 2015;49:67-81.
[24] Clinical Trials.gov. A study to evaluate the long-term safety and tolerability of Vabysmo in participants with nAMD (AVONELLE-X). [Internet; cited July 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT04777201.
[25] Clinical Trials.gov. A study to evaluate the long-term safety and tolerability of Vabysmo in participants with DME (Rhone-X). [Internet; cited July 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT04432831.
[26] Clinical Trials.gov. A study to investigate faricimab treatment response in treatment-naïve, underrepresented patients with DME (ELEVATUM). [Internet; cited July 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT05224102.
[27] APVRS. Design and rationale of the SALWEEN trial: A Phase IIIb/IV study of faricimab, a dual angiopoietin-2 and vascular endothelial growth factor-a inhibitor, in patients with polypoidal choroidal vasculopathy. [Internet; cited July 2024]. Available from: https://2022.apvrs.org/abstract/?code=200351.
[28] Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab in patients with choroidal neovascularisation secondary to pathologic myopia (POYANG). [Internet; cited July 2024]. Available from: https://www.clinicaltrials.gov/study/NCT06176352.
[29] Clinical Trials.gov. A real-world study to gain clinical insights into Roche ophthalmology products (VOYAGER). Internet; cited July2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT05476926.
[30] US FDA. Highlights of prescribing information, Susvimo. 2021. [Internet; cited July 2024]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761197s000lbl.pdf.
[31] Holekamp N, et al. Archway randomised Phase III trial of the Port Delivery System with ranibizumab for neovascular age-related macular degeneration (nAMD). Ophthalmology. 2021.

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