Diabetes Mellitus, Noninsulin-Dependent, 2

WHIPPANY, N.J.--( BUSINESS WIRE )--Detailed results from the Phase III FINEARTS-HF trial presented today at the European Society of Cardiology (ESC) Congress 2024 during a late-breaking Hot Line session and simultaneously published in the New England Journal of Medicine showed that KERENDIA ® (finerenone) achieved a statistically significant reduction of the composite of cardiovascular death and total (first and recurrent) heart failure (HF) events, defined as either an unplanned hospitalization for HF or an urgent HF visit, by 16% (rate ratio, 0.84; 95% confidence interval [CI], 0.74 to 0.95; P = 0.007) in patients with HF and a LVEF ≥40% (left ventricular ejection fraction) compared to placebo in addition to a patients’ prescribed treatment regimen. 1 KERENDIA is the first-and-only non-steroidal mineralocorticoid receptor antagonist (MRA) to meet a primary composite cardiovascular endpoint in a Phase III trial investigating patients with HF and LVEF ≥40%. 1 KERENDIA is currently approved to reduce the risk of cardiovascular death, hospitalization for HF, non-fatal myocardial infarction (MI), sustained eGFR decline, and end-stage kidney disease in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D). 2 KERENDIA already has established cardiovascular benefit (reduction in hospitalization for HF, CV death and non-fatal MI) in adults with CKD associated with T2D, 2 and this new data provides positive results in a different patient population not limited to CKD in T2D – patients diagnosed with HF (LVEF ≥40). 1 FINEARTS-HF is a multicenter, randomized, double-blind, parallel-group, placebo-controlled, event-driven Phase III trial. It is investigating the efficacy and safety of finerenone for the reduction of risk of cardiovascular death and HF events in patients with a diagnosis of symptomatic HF (New York Heart Association class II-IV) with a LVEF of ≥40%, a measurement that indicates how much blood the left ventricle of the heart pumps with each beat. 3 In the FINEARTS-HF trial, no new safety signals were identified compared with those seen in previous studies with the compound. 1 “ Treating heart failure patients with LVEF ≥40% has provided a challenge for many physicians, as these patients have a substantial risk for cardiovascular events. Unlike heart failure with reduced ejection fraction, there are limited guideline-directed options for heart failure with LVEF > 40%,” said Scott D. Solomon, MD, The Edward D. Frohlich Distinguished Chair, Professor of Medicine at Harvard Medical School, Director of Non-invasive Cardiology and Senior Physician at Brigham and Women’s Hospital and Chair of the trial’s Executive Committee. “ FINEARTS-HF is the first large-scale trial where a non-steroidal mineralocorticoid receptor antagonist met a primary composite cardiovascular endpoint in patients with heart failure with mildly reduced or preserved ejection fraction (LVEF > 40%), and these results provide insights for the cardiology community managing these high-risk patients.” “ Bayer has a strong heritage in cardiology, and heart failure is a key focus area for us, with these results underpinning our ongoing commitment to patients with this devastating condition. Based on FINEARTS-HF, KERENDIA has shown to reduce the risk of cardiovascular outcomes in a complex to treat patient population,” said Dr. Christian Rommel, Head of Research and Development at Bayer’s Pharmaceuticals Division. The results shown in the primary endpoint results were consistent across all prespecified subgroups. Secondary outcomes tested hierarchically included total number of worsening HF events (rate ratio, 0.82; 95% confidence interval [CI], 0.71 to 0.94, p=0.006) and the Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (TSS) assessed at months six, nine and 12. There was a mean change from baseline in the KCCQ-TSS of 8 points in the finerenone group and 6.4 points in the placebo group (between-group difference of 1.6 points; 95%CI, 0.8 to 2.3, p<0.001). Serious adverse events were comparable between treatment groups, occurring in 38.7% (1,157/2,993) of the finerenone group and 40.5% (1,213/2,993) of the placebo group. Discontinuation of the trial drug for reasons other than death was similar between groups, with 20.4% (611/2,993) in the finerenone group and 20.6% (616/2,993) in the placebo group. Increases in creatinine and potassium levels were more frequent in patients receiving finerenone compared to placebo, with investigator-reported hyperkalemia in 9.7% (289/2,993) of finerenone-treated patients versus 4.2% (125/2,993) in the placebo group. Serum potassium levels >6 mmol/L were observed in 3% (n=86) of the finerenone group compared to 1.4% (41/2,993) in the placebo group. While hyperkalemia was more common with finerenone, it rarely led to hospitalization (0.5% [16/2,993] versus 0.2% [6/2,993] in the placebo group), and no cases resulted in death. 1 HF is a complex clinical syndrome with symptoms and signs that result from any structural or functional impairment of ventricular filling or ejection of blood. 4 Approximately 6.7 million adults in the U.S. live with HF, of whom about 55% have a LVEF ≥40%.5 Despite the high prevalence, guideline-directed medical treatment options for patients with HF with LVEF ≥40% are limited. 6 This patient group is often balancing multiple comorbidities, such as obesity, hypertension and CKD. 4 Bayer plans to discuss this data and submission for regulatory approval with the U.S. Food and Drug Administration (FDA). About FINEARTS-HF 3 FINEARTS-HF is a randomized, double-blind, placebo-controlled, multicenter, event-driven Phase III trial investigating the efficacy and safety of KERENDIA ® (finerenone) for the reduction of risk of cardiovascular death and heart failure (HF) events in patients with a diagnosis of symptomatic heart failure (New York Heart Association class II-IV) with a left ventricular ejection fraction (LVEF) of ≥40%, measured by local imaging measurement within the last 12 months, who received diuretic treatment for at least 30 days prior to randomization. The primary endpoint of FINEARTS-HF was the composite of cardiovascular death and total (first and recurrent) HF events, defined as hospitalizations for HF or urgent HF visits. Approximately 6,000 patients were randomized to receive KERENDIA or placebo once daily for up to 42 months. Results showed that KERENDIA once daily in addition to a patients’ prescribed treatment regimen reduced the composite of total worsening HF events and cardiovascular death in patients with HF and mildly reduced or preserved ejection fraction. KERENDIA also significantly reduced the secondary endpoints of total HF events (HR 0.82 [95% CI, 0.71-0.94; p=0.0062]) and improved patient-reported health status as measured by the change from baseline in Total Symptom Score of Kansas City Cardiomyopathy Questionnaire (KCCQ-TSS) (between-group difference 1.6 points [95% CI, 0.8-2.3; p<0.0001]). With overall more than 15,000 patients, the MOONRAKER clinical trial program with KERENDIA, including FINEARTS-HF, is one of the largest HF trial programs to date and aims to establish a comprehensive body of evidence for KERENDIA across a broad spectrum of patients and clinical settings. 1 About KERENDIA ® (finerenone) 2 KERENDIA is a non-steroidal mineralocorticoid receptor antagonist (MRA) and was approved by the U.S. Food and Drug Administration (FDA) in July 2021 to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, non-fatal myocardial infarction, and hospitalization for HF in adults with CKD associated with T2D. In adults with CKD associated with T2D, KERENDIA has been recommended to reduce the risk of hospitalization for HF by the American Diabetes Association (ADA) 7 and European Society of Cardiology (ESC). 8 IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS: Concomitant use with strong CYP3A4 inhibitors Patients with adrenal insufficiency WARNINGS AND PRECAUTIONS: Hyperkalemia: KERENDIA can cause hyperkalemia. The risk for developing hyperkalemia increases with decreasing kidney function and is greater in patients with higher baseline potassium levels or other risk factors for hyperkalemia. Measure serum potassium and eGFR in all patients before initiation of treatment with KERENDIA and dose accordingly. Do not initiate KERENDIA if serum potassium is >5.0 mEq/L. Measure serum potassium periodically during treatment with KERENDIA and adjust dose accordingly. More frequent monitoring may be necessary for patients at risk for hyperkalemia, including those on concomitant medications that impair potassium excretion or increase serum potassium. MOST COMMON ADVERSE REACTIONS: From the pooled data of 2 placebo-controlled studies, the adverse reactions reported in ≥1% of patients on KERENDIA and more frequently than placebo were hyperkalemia (14% versus 6.9%), hypotension (4.6% versus 3.9%), and hyponatremia (1.3% versus 0.7%). DRUG INTERACTIONS: Strong CYP3A4 Inhibitors: Concomitant use of KERENDIA with strong CYP3A4 inhibitors is contraindicated. Avoid concomitant intake of grapefruit or grapefruit juice. Moderate and Weak CYP3A4 Inhibitors: Monitor serum potassium during drug initiation or dosage adjustment of either KERENDIA or the moderate or weak CYP3A4 inhibitor and adjust KERENDIA dosage as appropriate. Strong and Moderate CYP3A4 Inducers: Avoid concomitant use of KERENDIA with strong or moderate CYP3A4 inducers. USE IN SPECIFIC POPULATIONS: Lactation: Avoid breastfeeding during treatment with KERENDIA and for 1 day after treatment. Hepatic Impairment: Avoid use of KERENDIA in patients with severe hepatic impairment (Child Pugh C) and consider additional serum potassium monitoring with moderate hepatic impairment (Child Pugh B). Please click here for full Prescribing Information for KERENDIA. About Bayer’s Commitment in Cardiovascular and Kidney Diseases A leader in the cardiovascular (CV) space, Bayer upholds a long-standing commitment to delivering science for a better life by advancing research and treatment options. Bayer’s cardiorenal franchise, which began with the discovery and development of a number of vital therapies, now includes several products and compounds in various stages of preclinical and clinical development with the potential to impact the way that CV and kidney diseases are treated. Bayer is investigating potential treatment approaches for areas of high unmet medical need. Currently, Bayer is investigating nine CVR-related projects in different stages of development, including heart failure (HF) and non-diabetic chronic kidney disease (CKD). 9 Bayer is actively identifying resources and programs aimed at better understanding the real-world management of CKD, expanding screening and early care management for CKD, aligning with and supporting groups and institutions that share the common goals of improving health outcomes, promoting health literacy and education, and promoting research and initiatives that represent the diversity required to address the needs of all patients. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2023, the Group employed approximately 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 billion euros. For more information, go to www.bayer.com . Find more information at https://pharma.bayer.com/ Follow us on Facebook: http://www.facebook.com/bayer Follow us on X: @BayerPharma Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports, which are available on the Bayer website at www.bayer.com . The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. ____________________________ 1 Data on file. 2 Bayer Pharmaceuticals. Kerendia (finerenone) [package insert]. U.S. Food and Drug Administration. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215341s000lbl.pdf. Accessed August 30 , 2024. 3 Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone on Morbidity (Events Indicating Disease Worsening) & Mortality (Death Rate) in Participants With Heart Failure and Left Ventricular Ejection Fraction (Proportion of Blood Expelled Per Heart Stroke) Greater or Equal to 40% (FINEARTS-HF). Clinical trial registration No. NCT04435626. https://clinicaltrials.gov/study/NCT04435626 . Accessed August 30, 2024. 4 Heidenreich P, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol . 2023. https://pubmed.ncbi.nlm.nih.gov/35379503/ . Accessed August 30, 2024. 5 Bozkurt A, et al. Heart Failure Epidemiology and Outcomes Statistics: A Report of the Heart Failure Society of America. J Card Fail . 2023; Oct;29(10):1412-1451. doi: 10.1016/j.cardfail.2023.07.006. Epub 2023 Sep 26. PMID: 37797885; PMCID: PMC10864030. 6 Desai N, et al. Heart failure with mildly reduced and preserved ejection fraction: A review of disease burden and remaining unmet medical needs within a new treatment landscape. Heart Fail Rev . 2024;29(3):631-662. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11035416/ . Accessed August 30, 2024. 7 American Diabetes Association (Section 10: Cardiovascular disease and risk management: standards of care in diabetes—2024.). Diabetes Care . 2024;47(Suppl. 1):S179-S218. doi:10.2337/dc24-S010. 8 Marx N, et al. ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J . 2023;44(39):4043-4140. doi:10.1093/eurheartj/ehad192. 9 Bayer Pharmaceuticals. Development Pipeline. U.S. https://www.bayer.com/en/pharma/development-pipeline . Accessed August 30, 2024.

WHIPPANY, N.J--( BUSINESS WIRE )--Bayer will present late-breaking Phase III data from the FINEARTS-HF trial investigating KERENDIA ® (finerenone) in patients with heart failure (HF) and LVEF ≥40% (left ventricular ejection fraction), 1 at the European Society of Cardiology (ESC) Congress 2024. Additionally, the company will present results from FINE-HEART, an integrated, pooled, participant-level analysis across three pivotal Phase III clinical trials with finerenone—FINEARTS-HF, FIDELIO-DKD and FIGARO-DKD—that explored cardio-kidney outcomes in patients with HF with LVEF ≥40%, and/or chronic kidney disease (CKD) and type 2 diabetes (T2D). 2 Finerenone is marketed as KERENDIA ® and is currently approved to reduce the risk of cardiovascular death, hospitalization for HF, non-fatal myocardial infarction (MI), sustained eGFR decline and end-stage kidney disease in adult patients with CKD associated with T2D. 4 FINEARTS-HF Data Presentation FINEARTS-HF - Finerenone in heart failure with mildly reduced and preserved ejection fraction Hot Line 7, Session 11210 September 1, 2024, 6:00am EDT/11:00am BST The randomized, double-blind, placebo-controlled, event-driven Phase III trial investigated the efficacy and safety of finerenone for the reduction of risk of cardiovascular death and HF events in patients with a diagnosis of symptomatic heart failure (New York Heart Association class II-IV) with a LVEF of ≥40%. 1 Approximately 6,000 patients were randomized to receive either finerenone or placebo once daily for up to 42 months. 1 Earlier this month, Bayer announced that the FINEARTS-HF trial met its primary endpoint and achieved a statistically significant reduction of the composite of cardiovascular death and total (first and recurrent) HF events, defined as hospitalizations for HF or urgent HF visits. 2 KERENDIA is a non-steroidal, selective mineralocorticoid receptor antagonist (MRA) with established cardiovascular benefit (reduction in hospitalization for HF, CV death and non-fatal MI) in adults with CKD in T2D, 4 and this new topline data provided positive results in a different patient population not limited to CKD in T2D— patients diagnosed with HF (LVEF ≥40). 2 FINE-HEART Data Presentation 2 FINE-HEART - Participant-level pooled analysis of finerenone in heart failure and chronic kidney disease trials Hot Line 7, Session 11210 September 1, 2024, 6:44am EDT/11:44am BST FINE-HEART is an integrated, pooled, exploratory, participant-level analysis across three pivotal Phase III clinical trials with finerenone—FINEARTS-HF, FIDELIO-DKD and FIGARO-DKD— designed to explore its effect on cardio-kidney outcomes in patients with HF with LVEF ≥40%, and/or CKD and T2D. OCEANIC-AF Data Presentation 3 OCEANIC-AF - Asundexian versus apixaban in patients with atrial fibrillation Hot Line 6, Session 11209 September 1, 2024, 3:40am EDT/08:40 am BST The OCEANIC-AF Phase III trial is designed to investigate asundexian compared to apixaban, a direct oral anticoagulant, in patients with atrial fibrillation at risk for stroke. 3 Asundexian is an investigational agent and has not been approved by any health authority for use in any country for any indication. About KERENDIA ® (finerenone) 4 KERENDIA is a non-steroidal mineralocorticoid receptor antagonist (MRA) and was approved by the U.S. Food and Drug Administration (FDA) in July 2021 to reduce the risk of cardiovascular death, hospitalization for heart failure (HF), non-fatal myocardial infarction, sustained eGFR decline, and end-stage kidney disease and in adults with CKD associated with T2D. In adults with CKD associated with T2D, finerenone has been recommended to reduce the risk of hospitalization for HF by the American Diabetes Association (ADA) 5 and European Society of Cardiology (ESC). 6 IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS: Concomitant use with strong CYP3A4 inhibitors Patients with adrenal insufficiency WARNINGS AND PRECAUTIONS: Hyperkalemia: KERENDIA can cause hyperkalemia. The risk for developing hyperkalemia increases with decreasing kidney function and is greater in patients with higher baseline potassium levels or other risk factors for hyperkalemia. Measure serum potassium and eGFR in all patients before initiation of treatment with KERENDIA and dose accordingly. Do not initiate KERENDIA if serum potassium is >5.0 mEq/L. Measure serum potassium periodically during treatment with KERENDIA and adjust dose accordingly. More frequent monitoring may be necessary for patients at risk for hyperkalemia, including those on concomitant medications that impair potassium excretion or increase serum potassium. MOST COMMON ADVERSE REACTIONS: From the pooled data of 2 placebo-controlled studies, the adverse reactions reported in ≥1% of patients on KERENDIA and more frequently than placebo were hyperkalemia (14% versus 6.9%), hypotension (4.6% versus 3.9%), and hyponatremia (1.3% versus 0.7%). DRUG INTERACTIONS: Strong CYP3A4 Inhibitors: Concomitant use of KERENDIA with strong CYP3A4 inhibitors is contraindicated. Avoid concomitant intake of grapefruit or grapefruit juice. Moderate and Weak CYP3A4 Inhibitors: Monitor serum potassium during drug initiation or dosage adjustment of either KERENDIA or the moderate or weak CYP3A4 inhibitor and adjust KERENDIA dosage as appropriate. Strong and Moderate CYP3A4 Inducers: Avoid concomitant use of KERENDIA with strong or moderate CYP3A4 inducers. USE IN SPECIFIC POPULATIONS: Lactation: Avoid breastfeeding during treatment with KERENDIA and for 1 day after treatment. Hepatic Impairment: Avoid use of KERENDIA in patients with severe hepatic impairment (Child Pugh C) and consider additional serum potassium monitoring with moderate hepatic impairment (Child Pugh B). Please click here for full Prescribing Information for KERENDIA. About Bayer’s Commitment in Cardiovascular and Kidney Diseases A leader in the cardiovascular (CV) space, Bayer upholds a long-standing commitment to delivering science for a better life by advancing research and treatment options. Bayer’s cardiorenal franchise, which began with the discovery and development of a number of vital therapies, now includes several products and compounds in various stages of preclinical and clinical development with the potential to impact the way that CV and kidney diseases are treated. Bayer is investigating potential treatment approaches for areas of high unmet medical need. Currently, Bayer is investigating nine CVR-related projects in different stages of development, including heart failure and non-diabetic chronic kidney disease (CKD). 7 Bayer is actively identifying resources and programs aimed at better understanding the real-world management of CKD, expanding screening and early care management for CKD, aligning with and supporting groups and institutions that share the common goals of improving health outcomes, promoting health literacy and education, and promoting research and initiatives that represent the diversity required to address the needs of all patients. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2023, the Group employed approximately 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 billion euros. For more information, go to www.bayer.com . Find more information at https://pharma.bayer.com/ Follow us on Facebook: http://www.facebook.com/bayer Follow us on X: @BayerPharma Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports, which are available on the Bayer website at www.bayer.com . The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. 1 Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone on Morbidity (Events Indicating Disease Worsening) & Mortality (Death Rate) in Participants With Heart Failure and Left Ventricular Ejection Fraction (Proportion of Blood Expelled Per Heart Stroke) Greater or Equal to 40% (FINEARTS-HF). Clinical trial registration No. NCT04435626. https://clinicaltrials.gov/study/NCT04435626 . August 2024. 2 Data on File. 3 A Study to Learn How Well the Study Treatment Asundexian Works and How Safe it is Compared to Apixaban to Prevent Stroke or Systemic Embolism in People With Irregular and Often Rapid Heartbeat (Atrial Fibrillation), and at Risk for Stroke (OCEANIC-AF). Clinical trial registration No. NCT05643573. https://clinicaltrials.gov/study/NCT05643573 . August 2024. 4 Bayer Pharmaceuticals. Kerendia (finerenone) [package insert]. U.S. Food and Drug Administration. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215341s000lbl.pdf . August 2024. 5 American Diabetes Association (Section 10: Cardiovascular disease and risk management: standards of care in diabetes—2024.) Diabetes Care. 2024;47(Suppl. 1):S179–S218. doi:10.2337/dc24-S010. 6 Marx N, et al. ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J. 2023;44(39):4043-4140. doi:10.1093/eurheartj/ehad192. 7 Bayer Pharmaceuticals. Development Pipeline. U.S. Available at: https://www.bayer.com/en/pharma/development-pipeline . August 2024.

More than 90% of patients had absence of DME after four years in a pre-specified exploratory endpointPeople treated with Vabysmo sustained vision gains and anatomical improvements, with almost 80% receiving treatment at intervals of three or four months, in an exploratory analysis The study met all primary endpoints, showing safety data were consistent with Vabysmo’s known safety profileThis is the largest long-term extension dataset in DME to-date, demonstrating consistent positive results in a highly prevalent eye condition Basel, 17 July 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today new, four-year data from the RHONE-X extension study.1 The study met all primary endpoints, showing that Vabysmo® (faricimab) was well tolerated in people with diabetic macular edema (DME) who received treatment for up to four years.2 Exploratory results from the long-term study showed that Vabysmo continued to preserve vision, dry retinal fluid that can impair sight, and allow extended time between treatments in people with DME.2 These data were presented in a late-breaking oral presentation at The American Society of Retina Specialists (ASRS) 2024 Annual Meeting in Stockholm, Sweden.2 “These four-year data build on our pivotal studies and reinforce Vabysmo’s potential to become standard of care treatment for diabetic macular edema (DME), which affects 29 million people worldwide,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We are especially pleased to see that 9 out of 10 patients showed no sign of DME after four years of treatment with Vabysmo, which is an incredible long-term outcome for people living with this condition.” The RHONE-X study is the largest long-term extension dataset in DME, a leading cause of vision loss in people with diabetes.3,4 “I have been using Vabysmo as a first-line treatment for all the approved indications, including diabetic macular edema, and the positive long-term safety and efficacy results from the RHONE-X study are consistent with my clinical experience for over two years,” said study investigator Arshad M. Khanani, M.D., Director of Clinical Research at Sierra Eye Associates and Clinical Professor at the University of Nevada, Reno, who presented the data at the ASRS. During RHONE-X, all participants were treated with Vabysmo on a personalised treat-and-extend regimen, where the time between Vabysmo treatments could be increased based on retinal fluid levels and visual acuity. Results of the exploratory analysis showed that at the end of four years, nearly 80% of participants treated with Vabysmo had extended their treatment intervals to every three or four months. Additionally, people treated with Vabysmo maintained the vision improvements and sustained the drying of retinal fluid they achieved during the initial Phase III studies (YOSEMITE and RHINE). In a pre-specified exploratory endpoint, more than 90% of people treated with Vabysmo achieved absence of DME, defined as central subfield thickness (CST) less than 325 microns.2 CST is a measure of swelling from fluid in the back of the eye caused by unstable, leaky blood vessels; reducing CST indicates retinal drying. To date, Vabysmo is approved in nearly 100 countries for DME and neovascular or ‘wet’ age-related macular degeneration (nAMD).3,5-8 It is also approved in several countries, including the United States and Japan, for the treatment of macular edema following retinal vein occlusion.3,5,9 More than four million doses of Vabysmo have been distributed worldwide since its initial US approval in 2022.3 About RHONE-X1 RHONE-X is a multicentre two-year extension study designed to evaluate the long-term safety and tolerability of Vabysmo® (faricimab) in 1,474 patients with diabetic macular edema who completed one of the two Phase III studies, YOSEMITE (NCT03622580) or RHINE (NCT03622593).10,11 Patients in YOSEMITE and RHINE were treated with either Vabysmo or 2 mg aflibercept. Patients in RHONE-X were all treated with Vabysmo according to a personalised treatment interval. The primary objectives were to evaluate the long-term safety and tolerability of Vabysmo, including ocular adverse events (AEs), non-ocular AEs and presence of anti-drug antibodies. The study also had an exploratory objective to assess the long-term efficacy of Vabysmo. About diabetic macular edemaAffecting 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.12,13 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.14,15 The number of people with DME is expected to grow as the prevalence of diabetes increases.16 About the Vabysmo® (faricimab) clinical development programmeRoche 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).17 Roche has also initiated several Phase IV studies, including the ELEVATUM (NCT05224102) study of Vabysmo in underrepresented patient populations with diabetic macular edema, 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.18-20 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.21 About Vabysmo® (faricimab)Vabysmo is the first bispecific antibody approved for the eye.5,22 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.22,23 Vabysmo is approved in nearly 100 countries around the world, 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 the treatment of macular edema following retinal vein occlusion.3,5,9 Review by other health authorities is ongoing. 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 gene therapies and treatments across multiple vision-threatening conditions, including 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.24,25 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.5,22,23 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.3,5-9 Lucentis® (ranibizumab injection)* was the first treatment approved to improve vision in people with certain retinal conditions.26 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] 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 July 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT04432831.[2] Khanani, A.M. (2024, July 17). Four-year outcomes of faricimab in DME: First-time safety and efficacy results from the RHONE-X long-term extension trial. The American Society of Retina Specialists (ASRS) 2024 Annual Meeting in Stockholm, Sweden.[3] Roche data on file.[4] Lee, R., Wong, T.Y. & Sabanayagam, C. Epidemiology of diabetic retinopathy, DME and related vision loss. Eye and Vision 2, 17 (2015). https://doi.org/10.1186/s40662-015-0026-2. [5] United States (US) Food and Drug Administration (FDA). Highlights of prescribing information, Vabysmo. 2022. [Internet; cited July 2024]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761235s000lbl.pdf.[6] 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.[7] 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.[8] Chugai obtains regulatory approval for Vabysmo, the first bispecific antibody in ophthalmology, for neovascular or ‘wet’ age-related macular degeneration (nAMD) and DME. [Internet; cited July 2024]. Available from: https://www.chugai-pharm.co.jp/english/news/detail/20220328160002_909.html.[9] Chugai obtains regulatory approval for Vabysmo, the only bispecific antibody in the ophthalmology field, for additional indication of macular edema associated with retinal vein occlusion (RVO). [Internet; cited July 2024]. Available from: https://www.chugai-pharm.co.jp/english/news/detail/20240326160000_1054.html. [10] Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab in participants with DME (YOSEMITE). [Internet; cited July 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT03622580. [11] Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab in participants with DME (RHINE). [Internet; cited July 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT03622593.[12] 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. [13] The Lancet. Diabetes: A defining disease of the 21st century. Lancet. 2023 24;401(10394):2087.[14] All About Vision. Macula lutea. [Internet; cited July 2024]. Available from: https://www.allaboutvision.com/resources/macula.[15] National Eye Institute. Diabetic Retinopathy. [Internet; cited July 2024]. Available from: https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/diabetic-retinopathy.[16] Liu E, et al. DME: Clinical risk factors and emerging genetic influences. Clinical and Experimental Optometry. 2017;100:569–76. [17] 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.[18] 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. [19] 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.[20] 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 July 2024]. Available from: https://www.clinicaltrials.gov/study/NCT06176352. [21] Clinical Trials.gov. A real-world study to gain clinical insights into Roche ophthalmology products (VOYAGER). [Internet; cited July 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT05476926.[22] 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. [23] 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.[24] 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. [25] Holekamp N, et al. Archway randomised Phase III trial of the Port Delivery System with ranibizumab for nAMD. Ophthalmology. 2021.[26] 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. Roche Global Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58Sileia UrechPhone: +41 79 935 81 48Nathalie AltermattPhone: +41 79 771 05 25Simon GoldsboroughPhone: +44 797 32 72 915Karsten KleinePhone: +41 79 461 86 83Nina MählitzPhone: +41 79 327 54 74Kirti PandeyPhone: +49 172 6367262Yvette PetillonPhone: +41 79 961 92 50Dr. Rebekka SchnellPhone: +41 79 205 27 03Lorena CorfasPhone: +34 620 29 25 51 Roche Investor Relations Dr. Bruno EschliPhone: +41 61 68-75284e-mail: bruno.eschli@roche.comDr. Sabine BorngräberPhone: +41 61 68-88027 e-mail: sabine.borngraeber@roche.comDr. Birgit MasjostPhone: +41 61 68-84814e-mail: birgit.masjost@roche.com Investor Relations North America Loren KalmPhone: +1 650 225 3217 e-mail: kalm.loren@gene.com Attachment 17072024_Vabysmo RHONE-X data_EN