Two drugs that slow the progression of the most common cause of visual impairment in the elderly have been approved this year in the United States and are pending approval in Europe.
Its arrival will offer ophthalmologists a treatment option for the 400,000 people who each year develop an advanced form of AMD (pronounced demae, for the initials of age-related macular degeneration) in the European Union – almost 50,000 of them in Spain and 8,000 in Catalonia. But it places them before the challenge of identifying patients in whom the disease progresses more quickly and who can benefit most from treatment.
"AMD is a real epidemic," declares Jordi Monés, director of the Institut de la Màcula in Barcelona, who has participated in the clinical development of the new treatments. It is a progressive disease of the retina that affects one in four people over 60 in Europe, although most cases go undiagnosed. In 10% of those affected, or one in 40 people over the age of 60, AMD progresses to advanced forms in which patients suffer a significant loss of their visual ability.
“They lose the ability to distinguish details, so they cannot carry out such important activities as reading, driving or recognizing people's faces. They can distinguish light from darkness, but it is a disease that generates a significant disability", explains Monés, who points out that "AMD is the most common cause of blindness, although fortunately most cases do not reach this extreme" .
Some proteins in the immune system play a key role in the progression of the disease, according to fearsome research in recent years. The new drugs approved in the US have been designed to precisely inhibit two of these proteins.
Pegcetacoplan, marketed as Syfovre, inhibits the pro-inflammatory protein C3. It reduces the progression of AMD by nearly 20% within two years, according to two clinical trials published in October in which 1,258 patients participated. It has been authorized since February for the treatment of AMD in the US. In Europe, it has been authorized since 2021 for a rare hematological disease, paroxysmal nocturnal hemoglobinuria, but not yet for AMD.
Avacincaptad pegol, marketed as Izervay, inhibits a similar pro-inflammatory protein called C5. The Macula Institute was the first center in the world to apply it to patients in a phase 1 clinical trial in 2009. In another more advanced phase 3 clinical trial, it has shown that it slows the progression of the disease 14% within twelve months. It has been approved since the summer in the US.
Both drugs are administered by intraocular injections. Izervay must be injected every month, as it is the regimen that has shown effectiveness in the clinical trial, and the term can be extended to two months with Syfovre. The cost of treatment in the US is about $2,100 per injection with both products.
"These drugs will mean an important improvement for those patients in whom AMD has a faster evolution and who are destined to lose their vision if they do not receive any treatment", says Monés. On the contrary, "in patients in whom they evolve more slowly, it may be preferable not to apply the initial treatment. We are faced with the challenge of learning to individualize therapy".
When AMD affects the fovea – the region of the retina where visual acuity is greatest – its evolution is usually slower than when it originates outside the fovea. People who have extrafoveal AMD would therefore be better candidates to receive the new drugs, especially if they have already lost much of the vision in one eye and the AMD has started to affect the other as well.
But in the coming years "we hope to have new biomarkers obtained with artificial intelligence that will inform about the progression dynamics of AMD", Monés points out. In this way, "most ophthalmologists will be able to select the best treatment for each patient without needing to be experts in this disease as at present".
Syfovre and Izervay are the first drugs for the treatment of so-called dry or atrophic AMD, which represents 90% of all AMD cases. They are added to five drugs already approved for the treatment of wet AMD, which represents the other 10%.
