December 21, 2020: “Roche 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 personalised 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 randomised to receive either faricimab or aflibercept at fixed eight-week intervals, or faricimab at personalised 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 personalised 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.
Worldwide, an estimated 21 million people are living with DME, a leading cause of vision loss among working-age adults.
Whilst 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.
It has been almost a decade since a medicine with a new mechanism of action has been approved to treat DME.
Faricimab is the first investigational bispecific antibody designed for the eye. It targets two distinct pathways – via angiopoietin-2 (Ang-2) and VEGF-A – that drive a number of retinal conditions, including DME.
“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., Roche’s 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.
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.
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 studies
YOSEMITE (NCT03622580) and RHINE (NCT03622593) are two identical, randomised, multicentre, 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 personalised 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 personalised 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 around 21 million people globally, diabetic macular edema (DME) is a vision-threatening complication of diabetic retinopathy (DR).
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.
This leads to swelling, as well as blockage of blood supply to some areas of the retina.
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.
The number of people with DME is expected to grow as the prevalence of diabetes increases.
The condition is associated with blindness when left untreated and decreased quality of life.
There remains a significant unmet need for more effective, longer-lasting therapies for people with DME.
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.
Ang-2 and VEGF-A contribute to vision loss by destabilising blood vessels, causing new leaky blood vessels to form and increasing inflammation.
By independently blocking both pathways, faricimab is designed to stabilise blood vessels, potentially resulting in better vision outcomes, for longer, for people living with retinal conditions.”
https://www.roche.com/media/releases/med-cor-2020-12-21.htm