Geographic atrophy (GA) is the term used to describe advanced dry AMD and it is caused by the loss of central retinal tissue. Warning signs of GA can include loss of central vision and loss of contrast (shades of grey are difficult to distinguish). Approximately 10% of people with dry AMD will develop GA.

FACT OR FICTION: There’s Some Good News for Dry AMD Patients with Geographic Atrophy (GA)

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By Philip J. Rosenfeld, MD, PhD
Professor of Ophthalmology
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine
MVRF International Scientific Advisory Board Member

That’s a fact. There’s definitely good news for dry age-related macular degeneration (AMD) patients with geographic atrophy or GA, as it’s referred to in the clinic. It has always been true that GA progresses slowly, and patients with GA don’t have to get injections into their eyes as long as they stay dry. However, once they start developing wet AMD, which involves abnormal blood vessels growing in their macula, then they will need injections. Many of my patients with GA respond by asking, “Isn’t it better to have the wet AMD rather than the dry AMD; after all, the wet AMD can be treated with injections and the injections improve vision, right?” I explain that it’s not that simple, that dry and wet AMD aren’t two separate diseases, but rather different stages of the same disease. I explain that everyone with AMD starts with dry AMD and their disease progresses slowly over decades with only a minority of patients progressing from dry AMD to wet AMD. I tell them that, most likely, they’ll never need eye injections for wet AMD, and, by the way, not everyone sees better after getting the injections. I explain that the injections stop the rapid vision loss from wetAMD, and even if the injections are successful, the best-case scenario is that the injections convert the wet AMD back to dry AMD. I reassure my patients that it’s always better to have dry than wet AMD, but that’s a little misleading. While the good news for most AMD patients with early stage GA is that they don’t need injections, the bad news is that there’s no treatment for the GA, and over time, their vision will be worse. I explain that GA is the loss of tissue (photoreceptors) in the back of the eye, and once these cells are lost, they can’t regenerate. I explain further that GA will enlarge over time and more vision will be lost.

NOW THE GOOD NEWS: CLINICAL TRIALS FOR GEOGRAPHIC ATROPHY

Over the past few years, new therapies have been developed for the treatment of GA. Patients with GA have two options. They can remain uninvolved or they can get involved in clinical trials designed to test these novel therapies in the hope of slowing down their disease. In the past, clinical trials for wetAMD offered the opportunity for patients to receive novel, effective therapies years before they became commercially available. Those patients who participated in those trials, were able to save their vision. For this reason alone, patients with GA should participate in clinical trials once they understand the potential risks, as well as benefits. Currently, there are several promising therapies being investigated in ongoing clinical trials or in trials that will begin in the very near future.

CLINICAL TRIALS FOR PATIENTS WITH DRY AMD AND GEOGRAPHIC ATROPHY

The complement cascade is likely to play a major role in causing AMD. Studies have demonstrated a clear and unambiguous association between AMD and genes encoding complement proteins.This has led to strategies to inhibit complement activation by targeting complement proteins. 1 Most recently, a drug from Genentech/Roche known as FCFD4514S (lampalizumab) provided the first evidence that the growth of GA could be slowed down by complement inhibition. Lampalizumab inhibits Factor D, which is a rate-limiting enzyme involved in the activation of the alternative complement pathway. This drug is about to enter a large phase 2/3 trial and enrollment should be underway in the United States and other countries in the next few months. Patients interested in this therapy should contact their retinal specialist. Another complement inhibitor is LFG316, which is a fully human antibody that also targets the complement factor C5. A phase 1 dose escalation trial has been completed (NCT01255462), and a phase II trial (NCT01527500) to evaluate the ability of LFG316 to reduce the growth of GA with monthly intravitreal injections is ongoing with results expected in the second half of 2014. ORACEA® is a tetracycline derivative approved for treatment of inflammatory lesions of rosacea in adults and contains 30mg immediate and 10mg delayed release beads of doxycycline. However, this drug has other biological activities that are thought to be beneficial to AMD patients with GA. ORACEA® is given as a pill and is well tolerated with an excellent long-term safety profile and has demonstrated activity against molecular pathways that are suspected to be important in the evolution of dry AMD. A large clinical trial is currently underway.

SUMMARY

There are now exciting new options for AMD patients with GA. Since there are no treatments available for GA at this time, patients should seriously consider getting involved in one of these ongoing clinical trials. While being a clinical trial participant is not right for everyone, it does offer the best opportunity to get new therapies in the hope of slowing down their disease. Some patients are reluctant to participate because they don’t want to get a placebo. What they need to remember is that most studies offer a 50-66% chance of getting the experimental drug, and if they don’t participate in the trial, then they will be guaranteed to have a 0% chance of getting any novel therapy. Moreover, if they wait for the drug to get approved, it could take up to five years. By that time, it may be too late to save their central vision.

May 2014

References 1. Zhang K, Zhang L, Weinreb RN. Ophthalmic drug discovery: novel targets and mechanisms for retinal diseases and glaucoma. Nat Rev Drug Discov 2012;11(7):541-59. 2. Do DV, Pieramici DJ, van Lookeren Campagne M, et al. A phase ia dose-escalation study of the anti-factor D monoclonal antibody fragment FCFD4514S in patients with geographic atrophy. Retina 2014;34(2):313-20.