Genentech’s Faricimab Meets Primary Endpoint and Shows Strong Durability Across Two Global Phase III Studies for Diabetic Macular Edema, a Leading Cause of Blindness

Faricimab given every eight weeks and at personalized dosing intervals of up to 16 weeks demonstrated non-inferior visual acuity gains compared to aflibercept given every eight weeks in both studies

More than half of participants in the faricimab personalized dosing arms had extended time between treatments to 16 weeks at year one the first time this level of durability has been achieved in a Phase III diabetic macular edema study

Faricimab is the first investigational bispecific antibody designed for the eye and targets two distinct pathways – via angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A) – that drive a number of retinal conditions

Faricimab was generally well-tolerated, with no new safety signals identified

SOUTH SAN FRANCISCO, CA, USA I December 20, 2020 I Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY) today announced positive topline results from two identically designed global Phase III studies, YOSEMITE and RHINE, evaluating its investigational bispecific antibody, faricimab, in people living with diabetic macular edema (DME). Both studies met their primary endpoint and showed that faricimab given every eight weeks and at personalized dosing intervals of up to 16 weeks demonstrated non-inferior visual acuity gains compared to aflibercept given every eight weeks. Faricimab was generally well-tolerated with no new safety signals identified. The studies each have three treatment arms, with participants randomized to receive either faricimab or aflibercept at fixed eight-week intervals, or faricimab at personalized intervals of up to 16 weeks, following a loading phase.

In a secondary endpoint, across both studies, more than half of participants in the faricimab personalized dosing arms achieved an extended time between treatments of 16 weeks at year one. This is the first time any investigational medicine has achieved this level of durability in a Phase III study of people with DME.

In the United States, an estimated 750,000 people are living with DME, a leading cause of vision loss among working-age adults.1 While anti-vascular endothelial growth factor (VEGF) monotherapy injections have significantly reduced vision loss from DME, the treatment burden associated with frequent eye injections and physician visits can lead to under-treatment and, potentially, less than optimal vision outcomes.2,3 It has been almost a decade since a medicine with a new mechanism of action has been approved to treat DME.4 Faricimab is the first investigational bispecific antibody designed for the eye.5 It targets two distinct pathways – via angiopoietin-2 (Ang-2) and VEGF-A – that drive a number of retinal conditions, including DME.6

“These positive results show that faricimab has the potential to offer lasting vision improvements for people with diabetic macular edema, while also reducing the treatment burden associated with frequent eye injections,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We look forward to discussions with global regulatory authorities, with the aim of bringing this potential new treatment option to people with this condition as soon as possible.”

In addition to the YOSEMITE and RHINE studies, the Phase III Rhone-X study is investigating the long-term safety and tolerability of faricimab for the treatment of DME.7 Faricimab is also being studied in the Phase III TENAYA and LUCERNE studies as a potential treatment for neovascular or “wet” age-related macular degeneration (nAMD), an advanced form of AMD, which can cause rapid, severe and irreversible vision loss.8,9,10,11 Detailed results from the YOSEMITE and RHINE studies will be presented in February at Angiogenesis, Exudation, and Degeneration 2021 , a medical symposium presented by Bascom Palmer Eye Institute of the University of Miami Miller School of Medicine and submitted for approval for the treatment of DME around the world.

About the YOSEMITE and RHINE Studies5,12,13
YOSEMITE ( NCT03622580) and RHINE (NCT03622593) are two identical, randomized, multicenter, double-masked, global Phase III studies, evaluating the efficacy and safety of faricimab compared to aflibercept in 1,891 people living with diabetic macular edema (940 in YOSEMITE and 951 in RHINE). The studies each have three treatment arms: faricimab 6.0 mg administered at personalized dosing intervals of up to 16 weeks; faricimab 6.0 mg administered at fixed eight-week intervals; aflibercept 2.0 mg administered at fixed eight-week intervals. In all three arms, sham injections were administered at study visits when treatment injections were not scheduled, to maintain the masking of investigators and participants.

The primary endpoint of the studies is the average change in best-corrected visual acuity (BCVA) score (the best distance vision a person can achieve – including with correction such as glasses – when reading letters on an eye chart) from baseline at one year. Secondary endpoints include: safety; the percentage of participants in the personalized dosing arm receiving treatment every four, eight, 12 and 16 weeks, at week 52; the percentage of participants achieving a two-step or greater improvement from baseline in diabetic retinopathy severity at week 52; the percentage of participants achieving a gain of at least 15 letters in BCVA from baseline over time; the percentage of participants avoiding a loss of at least 15 letters in BCVA from baseline over time; and change in central subfield thickness from baseline over time.

About Diabetic Macular Edema
Affecting approximately 750,000 people in the United States, diabetic macular edema (DME) is a vision-threatening complication of diabetic retinopathy (DR).1,14 DR occurs when damage to blood vessels and the formation of new blood vessels causes blood and/or fluid to leak into the retina – a part of the eye that sends information to the brain, enabling sight.14,15 This leads to swelling, as well as blockage of blood supply to some areas of the retina.15 DME occurs when the 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.14,16  The number of people with DME is expected to grow as the prevalence of diabetes increases.17 The condition is associated with blindness when left untreated and decreased quality of life.14,18 There remains a significant unmet need for more effective, longer-lasting therapies for people with DME.3

About faricimab
Faricimab is the first investigational bispecific antibody designed for the eye.5 It targets two distinct pathways – via angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A) – that drive a number of retinal conditions.6 Ang-2 and VEGF-A contribute to vision loss by destabilizing blood vessels, causing new leaky blood vessels to form and increasing inflammation.3 By independently blocking both pathways, faricimab is designed to stabilize blood vessels, potentially resulting in better vision outcomes, for longer, for people living with retinal conditions.3

About Genentech in Ophthalmology
Genentech is researching and developing new treatments for people living with a range of eye diseases that cause significant visual impairment and blindness, including wet age-related macular degeneration (AMD), diabetic macular edema (DME), diabetic retinopathy (DR), geographic atrophy (GA) and other retinal diseases. The company is also investigating platforms for sustained ocular drug delivery, including Port Delivery System with ranibizumab (PDS), and faricimab, a bispecific antibody for the treatment of retinal eye diseases.

About Genentech
Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

1 Bressler NM, Varma R, Doan Q, et al. Underuse of the Health Care System by Persons With Diabetes Mellitus and Diabetic Macular Edema in the United States. JAMA Ophthalmology. 2014 Feb;132(2):168-73.

2 Zhao Y, Singh, RP. The role of anti-vascular endothelial growth factor (anti-VEGF) in the management of proliferative diabetic retinopathy. Drugs in Context. 2018;7:212532.

3 Sahni J, et al. Simultaneous inhibition of angiopoietin-2 and vascular endothelial growth factor-A with faricimab in diabetic macular edema. American Academy of Ophthalmology. 2019;126:1155–70.

4 FDA. Highlights of prescribing information, Lucentis. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125156s0069s0076lbl.pdf. Accessed November 2020.

5Roche/Genentech data on file.

6 Khan M, et al. Targeting Angiopoietin in retinal vascular diseases: A literature review and summary of clinical trials involving faricimab. Cells. 2020;9(8):1869.

7 Clinical Trials.gov. A study to evaluate the long-term safety and tolerability of faricimab in participants with diabetic macular edema (Rhone-X). Available at: https://clinicaltrials.gov/ct2/show/NCT04432831. Accessed November 2020.

8 Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab in participants with neovascular age-related macular degeneration (TENAYA). Available at: https://clinicaltrials.gov/ct2/show/NCT03823287. Accessed November 2020.

9 Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab in participants with neovascular age-related macular degeneration (LUCERNE). Available at: https://clinicaltrials.gov/ct2/show/NCT03823300. Accessed November 2020.

10 Pennington KL, DeAngelis MM. Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors. Eye and Vision. 2016;3:34.

11 Little K., et al. Myofibroblasts in macular fibrosis secondary to neovascular age-related macular degeneration-the potential sources and molecular cues for their recruitment and activation. EBioMedicine. 2018;38:283-91.

12 Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab (RO6867461) in participants with diabetic macular edema (YOSEMITE). Available at: https://clinicaltrials.gov/ct2/show/NCT03622580. Accessed November 2020.

13 Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab (RO6867461) in participants with diabetic macular edema (RHINE). Available at: https://clinicaltrials.gov/ct2/show/NCT03622593. Accessed November 2020.

14 National Eye Institute. Facts about diabetic eye disease. Available at:https://nei.nih.gov/health/diabetic/retinopathy. Accessed November 2020.

15 American Optometric Association. Diabetic retinopathy. Available at: https://www.aoa.org/healthy-eyes/eye-and-vision-conditions/diabetic-retinopathy. Accessed November 2020.

16 All About Vision. Macula Lutea. Available at: https://www.allaboutvision.com/resources/macula. Accessed November 2020.

17 Liu E, et al. Diabetic macular oedema: clinical risk factors and emerging genetic influences. Clinical and Experimental Optometry. 2017;100:569-76.

18 Park SJ, et al. Extent of exacerbation of chronic health conditions by visual impairment in terms of health-related quality of life. JAMA Ophthalmol. 2015;133:1267–75.

SOURCE: Genentech

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