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Roche’s competition in the eye disease space is intensifying with Regeneron’s high-dose Eylea and a looming biosimilar challenge, but the Swiss pharma said its blockbuster eye drug Vabysmo is holding strong. “We’re extremely pleased with the momentum that we see with Vabysmo in the US market and we would expect to see that to continue, especially given that we’ve just introduced the pre-filled syringe,” Roche’s pharma chief Teresa Graham said in a media call Wednesday. The company has already seen 80% conversion to the pre-filled syringe from the original vial packaging, she added. But the entrance of Eylea biosimilars could challenge Vabysmo’s momentum. On Tuesday, Amgen said it is moving forward with the launch of its Eylea biosimilar called Pavblu following an appeals court decision against Regeneron. A Roche spokesperson told Endpoints News in an email that the company is “prepared for market entry [of biosimilars] under any timing.” While Eylea blocks VEGF and PlGF, Roche’s drug acts on VEGF and Ang-2, which is a protein that helps regulate vascular remodeling and inflammation. Vabysmo’s “unique mechanism of action, the high level of drying that we’re seeing and the durability positions it extremely well against all of the products that are currently in the market,” Graham said. The pre-filled Vabysmo syringe won FDA approval in July for wet age-related macular degeneration, diabetic macular edema and macular edema following retinal vein occlusion, offering a ready-to-use alternative to the Vabysmo vials. The drug’s third-quarter sales reached CHF 1 billion ($1.6 billion), up 59% from the same time last year. Last year, the FDA greenlit Regeneron’s high-dose version of Eylea for wet AMD, DME and diabetic retinopathy. That same year, the Eylea franchise reached $5.9 billion in sales, which was significantly ahead of Vabysmo’s CHF 2.4 billion ($2.8 billion). Roche’s drug was later to market than Eylea. Nonetheless, Vabysmo shot to blockbuster status during its first full launch year after an approval in 2022. As for Roche’s pipeline, the company dropped several early- to mid-stage programs, including its PD-1xLAG3 antibody tobemstomig, which was in Phase 2 development for solid tumors. Other cuts included Phase 1 multiple myeloma asset forimtamig and some candidates for hepatitis B. The Swiss drugmaker said it is still interested in anti-tau approaches in Alzheimer’s disease, despite ending its partnership with UCB for a tau-targeting antibody. Graham described the termination as a “portfolio prioritization-driven decision.” The company’s Genentech unit is working with Sangamo to develop an epigenetic repressor to prevent the production of tau protein.

iStock, Robert Way Jefferies analyst Peter Welford noted that Roche’s pharma group came just slightly ahead of consensus expectations, driven by strong performance of its multiple sclerosis therapy Ocrevus and eye injection Vabysmo. Roche on Wednesday released its third-quarter earnings report , posting nearly $17.5 billion in sales, representing 9% year-on-year growth and exceeding Wall Street expectations. According to Jefferies analyst Peter Welford, Roche’s Q3 sales were 1% ahead of the consensus estimate. The company’s pharmaceuticals division, which remains its strongest unit with $13.4 billion in the quarter, beat analysts’ expectations by 2%. Roche’s top-performing asset in the quarter was the multiple sclerosis drug Ocrevus, which grew 11% to bring in almost $2 billion. Despite mounting biosimilar competition in the eye diseases space, Roche’s intravitreal injection Vabysmo continues its strong market momentum. The age-related macular degeneration (AMD) treatment surged 59% year-over-year, bringing in nearly $1.2 billion in Q3. Vabysmo, a dual inhibitor of VEGF and angiopoietin-2, is also indicated for diabetic macular edema (DME). In May 2024, the FDA greenlit two biosimilars to Regeneron’s blockbuster therapy Eylea—Samsung Bioepis and Biogen’s Opuviz and Biocon Biologics’ Yesafili—which are expected to compete with Vabysmo in the AMD and DME markets. On the negative side of the Q3 ledger, Roche’s PD-L1 antibody Tecentriq was “weak” in the quarter, according to Jefferies’ Welford, noting that its sales of just over $1 billion fell short of consensus estimates. Looking forward to the rest of the year, Roche reiterated its business outlook with growth of around mid-single-digit in group sales and in the high-single-digit range for core earnings-per-share. Opposition to Novo-Catalent Deal On the M&A front, Roche is urging regulatory authorities to block Novo Holdings’ proposed $16.5 billion acquisition of CDMO giant Catalent, arguing that the deal would have wide-ranging negative effects on the industry. “Limiting the competition in this space is not a good idea,” Roche CEO Thomas Schinecker said in a media call Wednesday morning, however insisting that the company itself would not be affected by the merger, according to Reuters . The acquisition would further restrict the contract manufacturing ecosystem, Schinecker said, which “could be a problem for other smaller players.” “From an industry perspective, it would be a wrong decision by authorities” if they let the transaction proceed, according to Schinecker. Pressure on the deal has been mounting. Last week, more than 10 unions, consumer organizations and public interest groups wrote to the Federal Trade Commission , urging the antitrust watchdog to “challenge” the proposed acquisition and to ensure that “competition is protected.” Sen. Elizabeth Warren (D-Mass.) earlier this month also flagged potential anti-competitive concerns with the transaction. In a letter to the FTC, Warren warned that the acquisition of contract manufacturer Catalent could increase Novo Nordisk’s dominance over the hot GLP-1 market, reducing competition and increasing prices. Referring to rival Eli Lilly, Warren said the deal could give Novo Nordisk “unprecedented visibility into and control over its competitor’s production capacity, costs, and business practices,” as well as “the ability to preference its own products and obstruct its competitors’ use of Catalent to produce GLP-1 drugs.” Lilly CEO David Ricks said in a Q2 earnings call in August that the company remains concerned about the Novo-Catalent deal. “We do rely on one of the Catalent sites for GLP-1 and other diabetes production,” Ricks told analysts. “We’ve aired those concerns publicly and privately since the proposed transaction was announced, and we’re waiting to see what happens.”

The ELEVATUM study showed clinically meaningful improvement in vision and reduction in retinal fluid in people with diabetic macular edema (DME) treated with Vabysmo who identify as African American, Black, Hispanic and Latino1 Efficacy and safety from this phase IV study were consistent with data from the Vabysmo phase III DME studies1These racial and ethnic groups are disproportionately affected by diabetes and at higher risk of developing DME, a leading cause of vision loss2-3 Basel, 18 October 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today positive topline one-year results from the open-label, single-arm phase IV ELEVATUM study evaluating Vabysmo® (faricimab) for the treatment of diabetic macular edema (DME) in people from racial and ethnic groups that are often underrepresented in clinical trials.4 Initial data from 124 participants in the United States (US) showed that after one year of treatment with Vabysmo, administered every eight weeks, participants could read an additional 12.3 letters on average – equivalent to about two and a half lines on an eye chart. Results among major racial and ethnic groups represented in this study were similar. Hispanic and Latino participants started the study with the most severe disease and had an average vision gain of 14.1 letters from baseline at one year, equivalent to nearly three lines on an eye chart. African American and Black participants gained an average of 11.3 letters from baseline at one year. Vabysmo was well tolerated, with no new safety events identified.1 These data were presented in a late-breaking oral presentation at the American Academy of Ophthalmology (AAO) 2024 Annual Meeting in Chicago, Illinois, on 18 October.1 The study is the first retina trial for historically underrepresented populations. “Vabysmo has been shown to be an effective first-line treatment for diabetic macular edema, and for the first time, we have data specifically demonstrating its ability to improve vision in Black, African American, Hispanic and Latino patients who are disproportionately impacted by this condition,” said investigator Jeremiah Brown, M.D., of Retina Consultants of Texas, who presented the data at AAO. “As a clinician who serves patients from these communities that are so often underrepresented in clinical trials, I believed it was important to take part in this groundbreaking study, and hope the findings will inform and improve the care we provide to our patients in the clinic daily.” Results were consistent with the phase III YOSEMITE and RHINE DME studies.5 A secondary endpoint showed robust retinal drying with Vabysmo across these racial and ethnic groups, who, on average, achieved a decrease of 206.3 microns in central subfield thickness (CST) from baseline.1 Reducing CST indicates retinal drying, which is an important clinical measure, as swelling from excess fluid in the back of the eye is associated with distorted and blurred vision.6 “We established ELEVATUM to specifically evaluate Vabysmo in underrepresented populations,” said Nilesh Mehta, Roche’s Global Therapeutic Area Head for Ophthalmology. “Including diverse populations and perspectives is part of our broader Roche Diversity, Equity & Inclusion (DE&I) strategy and is essential if we want to improve scientific understanding of diabetic macular edema and ultimately improve standard of care for all people living with this condition.” Among the 124 patients, 45% self-identified as Hispanic or Latino, and 48% as Black or African American.1 The study was designed to facilitate enrolment and promote retention of underrepresented patients. For example, ELEVATUM was conducted at sites that treat a high proportion of these populations in urban, rural and community-based locations. In addition, eligibility criteria allowed participants with a haemoglobin A1c (HbA1c) level up to 12%.4 An HbA1c test measures a person’s average blood sugar levels over the past three months and is used to diagnose diabetes.7 Typically, the threshold for DME trials is an HbA1c level of 10%. However, HbA1c levels can be higher in Black, African American, Hispanic and Latino populations compared with Caucasians, meaning a lower HbA1c threshold can inadvertently lead to the exclusion of patients from various ethnic and racial groups.8-9 To date, Vabysmo is approved in more than 100 countries for DME and neovascular or ‘wet’ age-related macular degeneration, and in over 30 countries for macular edema following retinal vein occlusion (RVO). More than five million doses of Vabysmo have been distributed globally since its initial US approval in 2022.10-15 About ELEVATUM4 ELEVATUM (NCT05224102) is a phase IV, multicentre, open-label, single-arm study designed to evaluate Vabysmo® (faricimab) as a treatment for diabetic macular edema (DME) in patients that have been historically underrepresented in clinical trials, including people who self-identify as Black, African American, Hispanic or Latino. Trial participants have not been treated with an anti‑vascular endothelial growth factor before the study. They receive treatment every four weeks with Vabysmo up to week 20, followed by treatment every eight weeks up to week 52. The primary endpoint is change from baseline in best corrected visual acuity at week 56. Secondary endpoints include safety and change in central subfield thickness from baseline over time. About Diabetic Macular Edema Affecting around 29 million people globally, diabetic macular edema (DME) is a vision-threatening retinal condition associated with blindness and decreased quality of life when left untreated.16-17 DME occurs when damaged blood vessels leak into and cause swelling in the macula – the central area of the retina responsible for the sharp vision needed for reading and driving.18-19 The number of people with DME is expected to grow as the prevalence of diabetes increases.20 About the Vabysmo® (faricimab) clinical development programmeRoche has a robust phase III clinical development programme for Vabysmo. The programme includes AVONELLE-X, an extension study of TENAYA and LUCERNE, evaluating the long-term safety and tolerability of Vabysmo in neovascular or ‘wet’ age-related macular degeneration (nAMD), and RHONE-X, an extension study of YOSEMITE and RHINE, evaluating the long-term safety and tolerability of Vabysmo in diabetic macular edema (DME).21-22 The POYANG study is evaluating Vabysmo in adult treatment-naive patients with choroidal neovascularisation secondary to pathologic myopia.23 Roche has initiated several phase IV studies, including the ELEVATUM study of Vabysmo in underrepresented patient populations with DME and the SALWEEN study of Vabysmo in a subpopulation of nAMD highly prevalent in Asia.4, 24 Roche has also initiated the VOYAGER study, a global real-world data collection platform, and supports several other independent studies to further understand retinal conditions with a high unmet need.25 About Vabysmo® (faricimab)Vabysmo is the first bispecific antibody approved for the eye.11, 26 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.5, 26 Vabysmo is approved in more than 100 countries around the world, including the United States (US), Japan, the United Kingdom and the European Union (EU) for people living with neovascular or ‘wet’ age-related macular degeneration and diabetic macular edema, and in more than 30 countries, including the US, EU and Japan, for people living with macular edema following retinal vein occlusion. Review by other health authorities is ongoing.10-15 About Roche in OphthalmologyRoche 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, and 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.27, 28 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.5, 11, 12, 26 Vabysmo is approved around the world for people living with nAMD, diabetic macular edema and macular edema following retinal vein occlusion.10-15 Lucentis® (ranibizumab injection)* was the first treatment approved to improve vision in people with certain retinal conditions.29 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. For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. 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] Emanuelli A. ELEVATUM, the First Industry Sponsored Trial Focused on Underrepresented Patients in Retina in the US. Presented at: American Academy of Ophthalmology (AAO) Annual Meeting; 2024, October 18; Chicago, IL, USA.[2] Coney J, Scott A. Racial disparities in the screening and treatment of diabetic retinopathy. Journal of the National Medical Association. 2022;114 (2):171-181.[3] Lee R, et al. Epidemiology of diabetic retinopathy, DME and related vision loss. Eye and Vision. 2015; 2, 17.[4] Clinical Trials.gov. A Study to Investigate Faricimab Treatment Response in Treatment-Naive, Underrepresented Patients With Diabetic Macular Edema (ELEVATUM) [Internet; cited October 2024]. Available from: https://www.clinicaltrials.gov/study/NCT05224102.[5] 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.[6] US National Institutes of Health - National Eye Institute. Macular edema. 2023. [Internet; cited October 2024]. Available from: https://www-nei-nih-gov.libproxy1.nus.edu.sg/learn-about-eye-health/eye-conditions-and-diseases/macular-edema.[7] Eyth E, Naik R. Hemoglobin A1C. 2023. [Internet; cited October 2024]. Available from: https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/books/NBK549816/.[8] Cavagnolli G, et al. Effect of ethnicity on HbA1c levels in individuals without diabetes: Systematic review and meta-analysis. PloS one. 2017;12 (2).[9] Borkar DS, et al. Understanding the impact of HbA1c thresholds on DME clinical trial eligibility by race. Presented at: AAO 2023; November 3-6, 2023; San Francisco, CA, USA. Poster PO492.[10] European Medicines Agency. Summary of product characteristics, Vabysmo. 2022. [Internet; cited October 2024]. Available from: https://www.ema.europa.eu/en/documents/product-information/vabysmo-epar-product-information_en.pdf.[11] US FDA. Highlights of prescribing information, Vabysmo. 2023 [Internet; cited October 2024]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761235s003lbl.pdf.[12] Medicines and Healthcare products Regulatory Agency approves faricimab through international work-sharing initiative. [Internet; cited October 2024]. Available from: https://www.gov.uk/government/news/mhra-approves-faricimab-through-international-work-sharing-initiative.[13] 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 October 2024]. Available from: https://www.chugai-pharm.co.jp/english/news/detail/20240326160000_1054.html.[14] Chugai obtains regulatory approval for Vabysmo, the first bispecific antibody in ophthalmology, for nAMD and DME. [Internet; cited October 2024]. Available from: https://www.chugai-pharm.co.jp/english/news/detail/20220328160002_909.html.[15] Roche data on file.[16] Im JHB, et al. Prevalence of DME based on optical coherence tomography in people with diabetes: a systematic review and meta-analysis. Survey of Ophthalmology. 2022 Jul-Aug;67(4):1244-1251.[17] The Lancet. Diabetes: A defining disease of the 21st century. Lancet. 2023 24;401 (10394):2087.[18] All About Vision. Macula lutea. [Internet; cited October 2024]. Available from: https://www.allaboutvision.com/resources/macula.[19] National Eye Institute. Diabetic Retinopathy. [Internet; cited October 2024]. Available from: https://www-nei-nih-gov.libproxy1.nus.edu.sg/learn-about-eye-health/eye-conditions-and-diseases/diabetic-retinopathy.[20] Liu E, et al. DME: Clinical risk factors and emerging genetic influences. Clinical and Experimental Optometry. 2017;100:569–76.[21] Clinical Trials.gov. A study to evaluate the long-term safety and tolerability of Vabysmo in participants with nAMD (AVONELLE-X). [Internet; cited October 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT04777201. [22] Clinical Trials.gov. Clinical Trials.gov. A study to evaluate the long-term safety and tolerability of Vabysmo in participants with diabetic macular edema (DME) (RHONE-X). [Internet; cited October 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT04432831.[23] Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab in patients with choroidal neovascularization secondary to pathologic myopia (POYANG). [Internet; cited October 2024]. Available from: https://www.clinicaltrials.gov/study/NCT06176352.[24] 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 October 2024]. Available from: https://2022.apvrs.org/abstract/?code=200351.[25] Clinical Trials.gov. A real-world study to gain clinical insights into Roche ophthalmology products (VOYAGER). [Internet; cited October 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT05476926.[26] Heier JS, et al. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for nAMD (TENAYA and LUCERNE): two randomised, double-masked, phase III, non-inferiority trials. The Lancet. 2022; 399:729-40.[27] US FDA. Highlights of prescribing information, Susvimo. 2021. [Internet; cited October 2024]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761197s000lbl.pdf.[28] 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.[29] US FDA. Highlights of prescribing information, Lucentis. 2014. [Internet; cited October 2024]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125156s0069s0076lbl.pdf. Roche Global Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58 Sileia UrechPhone: +41 79 935 81 48 Nathalie AltermattPhone: +41 79 771 05 25 Lorena CorfasPhone: +41 79 568 24 95 Simon GoldsboroughPhone: +44 797 32 72 915 Karsten KleinePhone: +41 79 461 86 83 Nina MählitzPhone: +41 79 327 54 74 Kirti PandeyPhone: +49 172 6367262 Yvette PetillonPhone: +41 79 961 92 50 Dr. Rebekka SchnellPhone: +41 79 205 27 03 Attachment 18102024_MR_Vabysmo ELEVATUM study _en