Currently, many patients with wet age-related macular degeneration (AMD) require monthly injections into the eye to preserve their vision. Those with advanced dry AMD, also called geographic atrophy (GA), have no effective treatments available to them. Fortunately, AMD research and drug developments are advancing rapidly to bring patients better treatments.
Wet Age-Related Macular Degeneration
For wet AMD, the standard treatments are intraocular injections of drugs that block vascular endothelial growth factor (VEGF). These drugs (Eylea®, Lucentis®, or Avastin®) typically work for 4-8 weeks, and then need to be injected again. Several new approaches to VEGF inhibition should reduce the injection frequency.
The rigid port delivery system (RPDS), is a device implanted into the wall of the eye in the operating room that can store, and slowly release, Lucentis. The delivery system is in a phase II clinical trial, called LADDER, with an expected completion date in mid-2019. This approach may result in fewer office visits and treatments. Once the RPDS runs out of Lucentis, it can be refilled during an office visit.
Brolucizumab is a new anti-VEGF drug that, in phase III clinical trials, can last as long as 12 weeks between treatments. FDA approval is expected in 2019.
Abicipar is another drug that is injected into the eye to target VEGF. A phase II trial shows it can last as long as 12 weeks.
RGX-314 is an anti-VEGF treatment delivered by gene therapy. It has the potential to block VEGF for years following a surgical procedure in which a harmless virus, called adeno-associated virus (AAV), carrying the anti-VEGF gene, is injected under the retina. This approach is more promising now that retinal AAV gene therapy has been approved by the FDA for another disease called Leber’s congenital amaurosis.
Another drug that blocks VEGF, by inhibiting its receptor, is called Sunitinib. One version is injected into the eye in the form of a sustained release depot (GB-102), while another version of this VEGF receptor inhibitor (X-82) is delivered orally. These drugs, which are in phase II trials, may work alone or in combination with other drugs injected into the eye.
Another drug (OPT-302) targeting new forms of VEGF, called VEGF C and D, is also in phase II trials, injected in combination with a traditional VEGF inhibitor.
Since VEGF isn’t the only protein that signals harmful blood vessels to grow and leak in wet AMD, several drugs targeting additional proteins are being tested in combination with anti-VEGFs. Dorzolamide-timolol (Cosopt®) is an eye drop used for glaucoma. Early results suggest these eye drops can decrease retinal fluid accumulation in wet AMD in combination with injected anti-VEGF drugs. This is now being tested in a phase III trial.
APL-2 and Zimura
An arm of the immune system, called the complement cascade, seems to promote wet AMD. So, a drug inhibiting the complement factor C3, called APL-2, is being injected with anti-VEGF drugs. This combination is in phase II trials. Avacincaptad pegol (Zimura®) is another drug targeting a different complement protein, C5.
RG7716 and REGN 910-3
Angiopoietin II is another protein that promotes wet AMD. This is being targeted in phase II trials by RG7716 and REGN 910-3. These are injected with an anti-VEGF drug. RG7716 is unique in that it’s a single antibody that targets both VEGF and Angiopoietin II. It has the potential to work better than drugs that target only one of these blood vessel growth-promoting proteins.
Also being targeted in clinical trials are the proteins endoglin, activin, and tissue factor. These proteins are involved in the growth of new blood vessels (angiogenesis), which is a key process involved in the development of the wet form of AMD.
Dry Age-Related Macular Degeneration
For patients with geographic atrophy (GA), there is currently no effective therapy. However, in a phase II trial, the complement C3 inhibitor Apl-2, significantly inhibited expansion of the area of atrophy. The drug is now advancing to phase III clinical trials. Apl-2 is injected into the eye either monthly or every other month. This drug is also being tested for wet AMD.
Zimura, a C5 inhibitor, is also being tested for GA by intraocular injection.
Several oral drugs are also being tested for GA. These include Oracea®, which is the antibiotic doxycycline. It has anti-inflammatory activities that may be beneficial for patients with geographic atrophy. This drug is in phase II/III clinical trials.
Another drug that is being explored that has anti-inflammatory properties is the diabetes medication metformin (Glumetza®, Glucophage®, Fortamet®, Riomet®, and Glucophage XR®).
A third oral drug being tested in GA patients is the antioxidant/iron chelator called lipoic acid. This drug was able to protect mice against retinal degeneration in my lab, and is retina-protective in several other preclinical models. This study is funded in part by BrightFocus Foundation.
Stem cells are also being injected into the eye in trials for GA. Some of these small trials suggest that this approach, if done correctly within clinical trials, can be safe and possibly helpful. Beware of clinics that offer stem cells therapy outside a clinical trial; several patients have lost vision after such treatments.
Overall, there is ample reason for optimism that improved treatments for AMD are on their way!
- Macular Degeneration Toolkit (Helpful Information to Understand and Manage Macular Degeneration)
- Expert Information on Macular Degeneration (Articles)
- BrightFocus Chats (Audio Presentations on Macular Degeneration)
- Clinical Trial Information for Macular Degeneration (Article)
- Treatments for Age-Related Macular Degeneration (Fact Sheet)
- What is Geographic Atrophy (Article)
- Clinical Trials for AMD: A BrightFocus Interview with Benjamin Kim, MD (Interview)
- Update on the Age-Related Macular Degeneration Drug Pipeline (Audio and Transcript)
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This content was last updated on: October 24, 2018
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