About Age-related Macular Degeneration
AMD affects the central part of the retina, known as the macula, leading to serious visual impairment and irreversible loss of central vision. The macular function is responsible for central vision and its sharpness is provided by the densely packed photoreceptor cells known as cones. The early stage of AMD is characterised by deposits called Drüsen, made up of A2E accumulation in particular, which only marginally affect vision. The patient gradually notices some deterioration in his/her central vision, which is then diagnosed by the ophthalmologist; this is the intermediate stage or age-related maculopathy (ARM). Later phases include two forms of AMD: wet AMD, also called exudative or neovascular AMD, characterised by the growth of choroidal neovessels in the subretinal space, or geographic atrophy (dry AMD), which is characterised by the loss of retinin pigment epithelium cells and photoreceptors which are the cells needed for the visual cycle. Dry AMD is much more common than wet AMD. The last stages of these two forms lead to the destruction of the neurosensory retina in the macular region; the progression of exudative (wet) AMD can lead to complete blindness within a few weeks, while the progression of dry AMD is generally slow.
AMD in its “wet” and “dry” forms currently affects 30 million people throughout the world. It is estimated that around 500,000 new cases of wet AMD are diagnosed every year throughout the world, and this figure is likely to increase dramatically as the population ages. It is estimated that more than 60 million people throughout the world, including 2 million in France, will be affected in 2050, making AMD a major health concern for elderly populations. The disease is rare before the age of 65, but its prevalence increases exponentially with age. The prevalence of the early stages is 1.6% in individuals over the age of 75, rising to almost 5% in those aged 75-84, and the frequency increases to 13% in persons aged 85 and over in the population studies. Legal blindness frequently develops over time, because the disease tends to become bilateral in 30% – 40% of patients within 5 years.
Serious visual impairment has an enormous impact on the quality of life. Individuals who present with a significant reduction in their visual acuity have limited ability to perform everyday tasks and their mobility is restricted as well. Patients with AMD claim that their general quality of life is 20%-25% below that of healthy elderly adults. Psychosocial distress is also associated with AMD, with higher numbers of patients suffering from emotional distress and depression than other elderly adults. The cost to society is only now beginning to be revealed.
MACA-PK is a randomised, double-blind, placebo-controlled study that will provide on one hand a phase 1 objective which consists of evaluating the safety and pharmacokinetics of Macuneos in 2 stages: Single Ascending Dose (SAD), then Multiple Ascending Dose (MAD). The SAD study will involve 32 healthy volunteers in 2 centers in Belgium, the MAD study will involve 32 healthy volunteers with a 14 days follow up in 2 centers in Belgium. The endpoints will be safety, pharmacokinetics, pharmacodynamics, measured through various plasmatic biomarkers.
The objective of MACA-INT is to determine the therapeutically effective dose of Macuneos in elderly persons suffering from the intermediate dry form of AMD in at least one eye (without loss of visual acuity) and who are likely to develop a severe form (exudative form or geographic atrophy). It is planned to be a multicentric, randomized double-blind, placebo-controlled study. That would involve 300 patients suffering of intermediate and late dry AMD, that will receive MACUNEOS at 100 mg, or 350 mg, and a placebo group. The planned duration of the study is 24 months with an interim analysis after 12 months. The primary endpoint will be atrophic lesions size progression, and the secondary endpoints, dark adaptation, accumulation of drusens, evolution towards wet AMD, and visual acuity.