The first drug for the treatment of geographic atrophy secondary to age-related macular degeneration may be approved this year
Geographic atrophy (GA), the chronic progressive degeneration of the macula as part of late-stage age-related macular degeneration (AMD), affects more than 8 million people worldwide — approximately 20% of all patients with AMD. The incidence of GA is expected to increase along with the aging population. Dry AMD is a leading cause of blindness and responsible for 90% of all AMD.
Up until now, our only options for slowing dry AMD from progressing to GA in one or both eyes were nutritional supplements. However, in November the FDA could approve the first injectable drug for slowing the progression of GA.
As I stated in a previous post, now is the time to begin educating patients about new therapies so they are aware and ready to come back to your clinic once the new treatments are approved and available. In my opinion, there is no patient education software that does a better job than Rendia to explain the eye’s anatomy to patients and potential outcomes of various treatment options.
Here’s a look at this innovative new therapy and how I use Rendia’s Exam Mode with my patients to show how it will work.
APL-2 Pegcetacoplan (Apellis)
As I said above, this novel agent may be the first drug approved for slowing progression of GA in dry AMD patients, which are the vast majority of people with AMD. While some GA can turn wet (~15%), most patients experience Retinal Pigment Epithelium (RPE) atrophy centrally, leading to blindness.
APL-2 would be the first drug approved for geographic atrophy from AMD.
Before APL-2, dry AMD treatment included vitamins such as AREDS II formulations for patients with intermediate-stage AMD or GA in one eye. These nutritional supplements have been studied for over 15 years and continue to show good outcomes in slowing the disease from progressing to GA in one or both eyes.
Once the central fovea shows atrophy, there is little that can be done. Since this drug could be approved as soon as November, it’s time to educate patients with non-foveal or early foveal involvement about this potential treatment option now.
Mechanism of Action
GA develops due to dysregulation of the complement cascade that has been implicated in GA pathogenesis and because all three complement pathways end in the central cleavage of C3, APL-2 is focusing on inhibiting C3 in the complement cascade. C3 is needed for the development of inflammation and formation of something known as a “membrane attack complex.” Pegcetacoplan is a highly selective bi-cyclic peptide conjugated to a PEG polymer that can block C3.
Clinical Results
In the clinical studies, pegcetacoplan resulted in statistically significant reductions in the growth of GA versus the sham at 12 months in the Oaks Study. A 29% reduction in GA progression was observed when the intravitreal injection was given every month and 20% reduction when given every other month. Combining Oaks with the Derby studies showed a 16% reduction versus sham in the monthly treatment group and 14% in the every-other-month group at 12 months, and 17% and 21% respectively between 12 and 18 months.
Most impressively, when analyzing patients with extrafoveal lesions only, the monthly treatment arm shows a 26% reduction in atrophy progression at one year and 23% reduction if administered every other month.
APL-2 does not reverse GA, but rather slows the advancement of the atrophy and hopefully delays central foveal involvement.
Adverse events include new onset exudative or wet AMD in 9.5% of patients given monthly injections and 6.2% for every other month, compared to 2.9% in the sham group.
How Exam Mode aids the doctor and patient in AMD education
I like to begin the patient education process by showing the illustration of the cross-section of the eye in Exam Mode. It orients the patient as to where the disease process is taking place. I then click the plus sign over the macular region. During this time I explain what we are looking at and how the normal anatomy of the layers of the retina should look.
On the left under Conditions you can click on “AMD (Dry)” which animates the formation of drusen. The circle on the right-hand side of the animation takes you to a straight-on view that displays geographic atrophy in the macular region. To the left on the animation line I can click “POV” and simulate what AMD/GA does to the patient’s central vision.
Using Rendia’ Exam Mode to visually explain AMD and GA improves patient comprehension and saves me several minutes per visit.
At this point, the patient fully and efficiently understands their condition. I’ve found that using Rendia will save me 3-5 minutes per patient explaining AMD/GA. I believe it’s because the patient is quickly able to understand where the condition is occurring and how it will eventually affect them.
Finally, I can discuss various existing treatments such as nutritional supplements like AREDS II or carotenoid formulations. And I can give patients hope that in the near future treatments designed to slow progression of dry AMD, such as APL-2, may be available.
Want to learn more about Exam Mode? Watch this explainer video about how Exam Mode saves time in my practice.