Update on the Age-Related Macular Degeneration Drug Pipeline

Scheie Eye Institute, University of Pennsylvania
A research scientist holding a vial of medication used to treat macular degeneration
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 are Beovu®, Eylea®, Lucentis®, or Avastin®.


Abicipar is another drug that is injected into the eye to target VEGF. Phase III trials showed that it can last as long as 12 weeks.

Port Delivery System

The port delivery system (PDS) is a device implanted into the wall of the eye during a surgical procedure that can store, and slowly release, Lucentis (ranibizumab).  This may result in fewer office visits and treatments. Once the PDS runs out of Lucentis, it can be refilled during an office visit. In a phase II clinical trial, patients receiving the highest Lucentis dose required refills once every 15 months on average.


Retinal gene therapy for AMD appears very promising now that retinal gene therapy has been approved by the FDA for another disease called Leber’s congenital amaurosis. 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 in the operating room. In a phase I/II trial with 42 patients, 9 of the 12 patients receiving the highest virus- dose did not require any further anti-VEGF injections in the six months following the RGX-314 injection. No drug-related serious adverse events were observed.


ADVM-022 is another AAV-anti-VEGF gene therapy, but in contrast to RGX-314, it is injected into the vitreous (which is the substance that fills in the region from the lens to the back of the eye), like Lucentis, Eylea, and Avastin. This means that it can be delivered in the office rather than the operating room. In a phase I trial with 6 patients, none has needed any further anti-VEGF injections in the six to ten months following ADVM-022 injection.


Another drug that blocks VEGF, by inhibiting its receptor, is called Sunitinib. One form is injected into the eye as a sustained release depot (GB-102) and lasted at least six months in a phase I/IIa clinical trial.


X-82, another VEGF receptor inhibitor, is delivered orally.  These drugs, which are in phase II trials, may work alone or in combination with other drugs injected into the eye.

Combination Drugs

Cosopt® (Dorzolamide-timolol) and Anti-VEGF Drugs

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. Cosopt® (Dorzolamide-timolol) 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. It may be particularly helpful in patients who don’t respond optimally to anti-VEGF drugs alone.

OPT-302 and Anti-VEGF Drugs

Another drug targeting new forms of VEGF, called VEGF C and D (OPT-302), is also in phase II trials, injected in combination with a traditional VEGF inhibitor. Results of this trial show that patients receiving monthly injections of OPT-302 in combination with Lucentis had better visual acuity outcomes than with Lucentis alone.

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.

Other Drug Developments

Also, being tested in clinical trials with wet AMD patients 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.

Advanced Dry Age-Related Macular Degeneration

For patients with advanced dry age-related macular degeneration, also called geographic atrophy (GA), there is currently no FDA-approved therapy. There are, however, several treatments that are currently in clinical trials.


However, in a phase II trial, the complement C3 inhibitor Apl-2 significantly inhibited expansion of the area of atrophy. Complement is an arm of the immune system that seems to be overactive in AMD. The drug is now in 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® (avacincaptad pegol), which inhibits another protein in the complement cascade, C5, is also being tested by intraocular injection for GA. In a phase II trial, it slowed the growth of GA.


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 trials.


Another drug with anti-inflammatory properties is the diabetes medication, metformin.A retrospective study of patients at the University of Florida found that patients taking metformin had a decreased risk of developing AMD.

Stem Cells

Stem cells are also being injected into the eye in trials for GA.  Some of these small trials suggest the approach if done correctly within clinical trials, can be safe and possibly helpful. Some of the transplants use cells layered on thin scaffolds, and others employ cells kept in a fluid suspension and injected under the retina. The addition of Rho-kinase inhibitors may help protect vision cells from damage induced by the surgical procedure. Beware of clinics that offer stem cell therapy outside a clinical trial; several patients have lost vision after such treatments.


This content was first posted on: December 30, 2019

The information provided here is a public service of the BrightFocus Foundation and should not in any way substitute for personalized advice of a qualified healthcare professional; it is not intended to constitute medical advice. Please consult your physician for personalized medical advice. BrightFocus Foundation does not endorse any medical product, therapy, or resources mentioned or listed in this article. All medications and supplements should only be taken under medical supervision. Also, although we make every effort to keep the medical information on our website updated, we cannot guarantee that the posted information reflects the most up-to-date research.

These articles do not imply an endorsement of BrightFocus by the author or their institution, nor do they imply an endorsement of the institution or author by BrightFocus.

Some of the content may be adapted from other sources, which will be clearly identified within the article.

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