Geographic Atrophy in a Clinical Trial Environment Thuy Chau Clinical Trials Research Centre

Background Age-related macular degeneration (AMD) is a progressive eye disease, which is the leading cause of irreversible blindness in people aged 50 years and older in the developed world (Friedman et al. 2004) http://macuclear.com/about/about-dry-amd/

What is Geographic Atrophy? Geographic atrophy represents the advanced/late form of dry AMD Development and gradual enlargement of one or more atrophic patches that involve the retinal pigment epithelium and overlying photoreceptors Pathophysiology is not well understood. The most common sequence according to the Age related Eye Disease Study (AREDS): Large drusen Hyperpigmentation of the RPE Regression of the drusen RPE cell death, hypopigmentation Development of atrophic area

What is Geographic Atrophy? GA often develops first in the region near the fovea, but not involving the foveal center. It progresses gradually over time, sparing the fovea until late in the course of the disease. Rate of GA enlargement has been 1-2.1 mm2/year (Age-Related Eye Disease Study [AREDS] Research Group, 2009; Holz et al, 2007) Schmitz-Valckenberg, S., Fleckenstein, M., Helb, H.-M. et al, In vivo imaging of foveal sparing in geographic atrophy secondary to age-related macular degeneration. Invest Ophthalmol Vis Sci. 2009;50:3915–3921.

Who does Geographic Atrophy impact? GA affects over 5 million people worldwide (Lancet Glob Health, 2014) Occurrence of GA increases exponentially with age Responsible for 10-20% of cases of blindness in AMD patients Both genetic and environmental factors may contribute to the development and progression of GA 1. Rudnicka A, et al. Ophthalmology 2012;119:571–80. 2. Wong et al, Lancet Glob Health 2014;2: e106–16

Treatment for GA Currently no approved medical treatments for Geographic Atrophy Clinical research studies and trials investigating ways to reduce the speed of GA progression Prof Robyn Guymer, the Clinical Trial Research Centre and the Macular Research Unit were involved in 5 pharma sponsored research studies, 1 study recruiting currently

Natural history studies: Treatment for GA Natural history studies: Natural History of a disease: “The natural course of a disease from the time immediately prior to its inception, progressing through its presymptomatic phase and different clinical stages to the point where it has ended and the patient is either cured, chronically disabled or dead without external intervention” Proxima A (Roche) Proxima B (Roche) Rational: to contribute further to community understanding of visual function and genetics in a broad population of GA patients 1 Posada de la Paz M; Groft SC. 2010. Rare diseases epidemiology. Vol. 686

Treatment for GA Clinical Trials: “Any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes” The World Health Organization (WHO) definition Beacon (Allergan) Lampalizumab & Lampalizumab Extension (Roche) Filly (Apellis) ISIS (Ionis Pharmaceuticals) Multicenter, randomized, double-masked, Sham treatment-controlled study Rational: to see whether these investigational drugs can reduce the speed of GA progression

Imaging Geographic Atrophy

Imaging Geographic Atrophy Fundus Autofluorescence (FAF)

Imaging Geographic Atrophy

Recruitment AMD Database Registry - http://www.cera.org.au/research/clinical-trials-research-centre

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