Apr 19, 2023

Geographic Atrophy: The Advanced Form of Dry AMD

Science Education

Geographic atrophy causes significant central vision loss and remains an unmet medical need.

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Age-related macular degeneration (AMD) is the leading cause of blindness for people 55 and older living in developed countries, affecting approximately 11 million people in the US and 170 million worldwide. Advanced cases of AMD cause central vision loss including the loss of the ability to read and recognize faces.

AMD is a complex disease with advancing age, a history of smoking, and genetics being major risk factors.

Researchers have determined that the complement system – part of the innate immune system which fights off bacteria and other pathogens – is overactive in people with AMD, leading to retinal degeneration.

Courtesy of Marco Zarbin, MD, PhD. A fundus photo of a retina affected by GA.

Virtually everyone who has AMD starts off with the dry form. The hallmark of dry AMD is the buildup of drusen deposits underneath or near the central region (macula) of the retina. These deposits are comprised of lipids (fats) and proteins. Many people develop drusen as they age. Certain types of drusen (the soft and large types) are more likely to lead to loss of retinal cells and vision loss.

In some cases, people with dry AMD develop wet AMD which is characterized by the growth of leaky, damaging blood vessels underneath the retina. People with wet AMD experience changes in vision relatively quickly – in a matter of weeks or even days. Retina doctors have injectable treatments that are FDA-approved for wet AMD and are most effective when administered at early stages of the condition.

Many people with dry AMD – the early and intermediate forms – never experience any significant vision loss. However, dry AMD can progress to an advanced condition known as geographic atrophy (GA) which often leads to significant central vision loss. Vision loss from GA is typically more gradual than it is from wet AMD. Approximately 5 million people around the world have GA with 1 million in the US affected.

GA is characterized by the loss of retinal pigment epithelial (RPE) cells which provide support for photoreceptors, the cells that make vision possible, as well as degeneration of the choriocapillaris, a layer of capillaries underneath the retina. Loss of the RPE cells and the choriocapillaris ultimately lead to loss of photoreceptors, and subsequently, central vision. People with GA develop what are known as scotomas, blind spots in or near their central field of vision. The scotomas grow in area over time causing more central vision loss.

In February 2023, SYFOVRETM became the first FDA-approved treatment for GA. Developed by Apellis, the therapy slows the growth rate of the lesions (regions of retinal cell degeneration) that lead to central vision loss. SYFOVRE is injected into the middle of the eye by a retinal specialist once every 25 to 60 days. The treatment works by inhibiting the C3 protein which is associated with an overactive and damaging innate immune system.

Iveric Bio is seeking FDA approval for its emerging GA treatment known as avacincaptad pegol, which slowed the growth rate of GA lesions in two Phase 3 clinical trials. The FDA's decision on avacincaptad pegol is expected by the end of August 2023. Also injected into the middle of the eye, the treatment works by inhibiting the C5 protein which is associated with an overactive and damaging innate immune system.