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Spotlight on Macular Degeneration

by | Jun 26, 2023 | Biotech for Non-Scientist

Getting old is for the birds. Time has its way with nearly every part of us: skin, hair, and muscles. Few changes are more alarming, however than those to our eyes. There’s more to old eyes than bifocals and cataracts, though. One of the most common eye diseases is age-related macular degeneration (AMD). It affects more than 13 million people over the age of 50 in the United States. It’s the leading cause of vision loss in this age group. Let’s review and explain the AMD and how the biopharma industry is working on treatments.

Eyes are spectacularly complicated organs: they contain over two million moving parts. You know some basics: iris, pupil, lens, retina. In some ways, this last, the retina, is more accurately considered part of the brain.


The retina is composed of light-sensitive nervous tissue, which forms a thin membrane that lines the rear two-thirds of the eyeball. It takes in light from the world around and converts it into neural signals that travel along the optic nerve to the brain, telling us—“Hey, there’s an apple, or a laptop, or whatever.”

The macula is the small central area of the retina that enables central, high-resolution color vision.


Macular degeneration progressively devastates eyesight, causing blurred vision and blocking the center of a person’s visual field. What begins as a minor annoyance makes everyday tasks such as reading and driving impossible.

Ophthalmologists and other scientists don’t know exactly what causes AMD. It is, however, associated with a buildup of proteins and lipids just beneath the retina. These deposits, drusen, are a normal part of aging. However, the presence of larger or more drusen raises the risk of AMD. As the disease progresses, vision decreases. There are two types of AMD: neovascular (wet) or atrophic (dry).


In wet AMD, the infiltration of excess blood vessels is the main culprit. These abnormal vessels often leak fluid and blood, injuring the retina. Wet AMD progresses quickly, leading to loss of central vision without treatment. This form of disease accounts for about 10 percent of cases.

FDA-approved treatments for wet AMD include Lucentis (Genentech; South San Francisco), Beovu (Novartis; Basel, Switzerland), Eylea (Regeneron Pharmaceuticals, Tarrytown, NY), and Faricimab (Genentech; South San Francisco). These work by mopping up excess vascular endothelial growth factor (VEGF), which causes excess blood vessel growth. Lucentis, Beovu, and Faricimab are monoclonal antibodies specific for VEGF. Eylea consists of the VEGF receptor fused to the constant region of an antibody for stability. Similar to a mAb, this combination is called a fusion protein. It’s highly specific for VEGF, binding it before it reaches its intended receptor on the surface of blood vessels. These VEGF-blocking treatments effectively stop the progression of AMD but don’t cure it.

Kodiak Sciences (Palo Alto, CA) is working on an antibody-biopolymer conjugate (ABC) called KSI-301, which also targets VEGF. An ABC is an antibody with a biopolymer—a chain of repeating subunits produced by a living organism—attached. In KSI-301, the repeating subunits are lipids. They make the antibody more stable. That means patients can go up to five months between injections, compared to one month (Lucentis), two months (Eylea), two to three months (Beovu), or three to four months Faricimab. The treatment is now in Phase III development.

These therapies are injected into the patient’s eye, which makes them understandably unappealing. As an alternative, PanOptica (Mount Arlington, NJ) is developing PAN-90806. Patients could administer this small molecule inhibitor of VEGF at home by eyedrop. The drug is now in Phase II clinical studies.

RegenxBio (Rockville, MD) aims to do away with repeated treatments altogether with gene therapy. RGX314 delivers a gene encoding an anti-VEGF antibody. In Phase I/II studies, participants produced the therapeutic protein, controlling VEGF levels. The treatment is now in Phase III development.


Dry AMD involves a gradual breakdown in the macula’s light-sensitive cells. The dry variety progresses much more slowly than the wet and accounts for about 90 percent of AMD cases. Advanced dry AMD occurs when cells in regions of the retina have wasted away and died. Sometimes these regions of atrophy (death) look like a map to the physician examining the retina, giving rise to the term “geographic atrophy” (GA) for late-stage dry AMD.
FDA approved a groundbreaking treatment for GA, an advanced form of AMD on February 17, 2023. The drug, named pegcetacoplan, is the first ever FDA-approved treatment for GA, which affects a significant portion of the population, both in the US and worldwide. Some studies suggest that high doses of antioxidants, including C and E vitamins, copper, zinc, and beta-carotene, may slow its progression.
Inflammation, specifically the activation of complement proteins, is associated with drusen buildup and dry AMD progression. When they’re activated, these immune system proteins interact, destroying targeted cells. Inappropriate activation of complement proteins can destroy healthy cells and tissue. Several drugs in clinical development work by inactivating complement proteins:

  • Apellis Pharmaceuticals’ (Crestwood, KY) peptide drug Pegcetacoplan (APL-2) is in Phase III development. APL2 binds to complement protein C3 and prevents its interaction with other complement proteins. Preventing this interaction impedes activating their destructive power. The FDA has now approved Apellis Pharmaceuticals’ complement protein C3 inhibitor pegcetacoplan for paroxysmal nocturnal haemoglobinuria (PNH) as of May 26, 2021.
  • IvERIC Bio’s (Princeton, NJ) DNA aptamer Zimura (avacincaptad pegol) was approved by FDA for the treatment of geographic atrophy in November 2022 after completing Phase III clinical trials. DNA aptamers are short strands of DNA that bind to a specific protein. Zimura binds to and inhibits complement protein C5.
  • Ionis’ (Carlsbad, CA) and Roche’s IONIS-FB-LRx is an antisense drug that blocks the production of complement factor B and is currently in Phase III clinical testing.

The National Eye Institute (NEI) started clinical testing of stem cells for dry AMD in 2020. In 2022, at NEI, the first U. S patient received the therapy as part of a clinical trial to use replacement tissues from patient-derived induced pluripotent stem (iPS) cells. Researchers have coaxed stem cells in the lab to grow into retinal cells. In rodent and pig models, these cells restored vision, setting the stage for testing in humans.


Most macular degeneration is connected to aging. However, Stargardt disease and other juvenile forms are associated with several different genes. Also referred to as macular dystrophy, all juvenile varieties are inherited. They have no cure or treatment. The therapies under development for dry AMD may also prove helpful in Stargardt disease.

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Author: Emily Burke, PhD
Editor: Sarah Van Tiems, MS
Scientific Review: Tahir Hayat, MS


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