For many patients with wet age-related macular degeneration (AMD), the anti-VEGF drugs have worked wonders. These medicines, which are injected into the eye, typically every 1-3 months, include brolucizumab (Beovu®), aflibercept (Eylea®), ranibizumab (Lucentis®) and Avastin® (bevacizumab),
They are called anti-VEGF because they work by blocking the activity of vascular endothelial growth factor (VEGF), a protein that promotes blood vessel growth.
They often protect the central vision in patients who, if they had the disease 10 years ago, might have lost their vision. However, the injections are not without problems. The burden of having an injection into the eye every month is significant. My patients always want to know when longer lasting drugs will be available.
On the Horizon
Sustained Release Lucentis
Now, there are several longer lasting versions on the horizon. Genentech, the maker of Lucentis, has a sustained release system that has completed a phase II clinical trial called LADDER, and enrolled 220 patients. The system has received “fast track” designation by the FDA, which could result in a faster approval. It is now in a phase III trial.
The device is implanted into the eye in a relatively simple operating room procedure. Most of the device resides inside the eye, and out of view. Part of it is flush with the eye wall (the sclera). Through this portion, an ophthalmologist can refill the device, using a technique similar to the current monthly injections. The results showed a similar response to monthly Lucentis injections, and patients receiving the highest dose needed drug refills only once every 15 months, on average. Five percent of patients had bleeding into the eye when the device was implanted, and this was only considered a serious complication in one patient. A few patients needed to have the device removed because of implantation or exposure problems.
Sustained Release Eylea
Regeneron, which makes Eylea, is also developing a sustained release system, but it is not yet in clinical trials. It involves incorporating Eylea into a gel, which, after injection into the eye, releases the drug slowly.
Another anti-VEGF drug with the potential to have longer-lasting effects is Abicipar, developed by Allergan in partnership with Molecular Partners. This protein is similar to an antibody and appears to remain in the eye for longer periods than the other anti-VEGF medications. Phase III trials show that Abicipar injected every 8 weeks, or even every 12 weeks, is not inferior to Lucentis injected every 4 weeks. The drug may become available in the second half of 2020.
Gene Therapy for Wet AMD
Another potential long-lasting approach to wet AMD is gene therapy. Recently, studies lead by Dr. Jean Bennett at the University of Pennsylvania have shown that retinal gene therapy for a rare hereditary disease is safe and effective, can least for years following a single injection, and was FDA approved. These studies pave the way for additional gene therapies for other retinal diseases. Early stage clinical trials have used adeno-associated virus to deliver genes encoding VEGF blockers similar to Lucentis and Eylea. One drug called RGX-314 is injected under the retina. In a phase I/2 trial, the therapy was safe and appeared to nearly eliminate the need for additional treatments over a one-year period. Another drug called ADVM-22 is injected into the vitreous jelly in the center of the eye instead of under the retina. This drug also dramatically reduced the need for additional treatments, but testing so far has only included a small number of patients and visual acuity results have been variable.
A Class that Failed
Unfortunately, another class of drugs that looked promising in phase II trials, and held out promise for less frequent injections, has now failed phase III trials. These drugs targeted platelet derived growth factor (PDGF), which is involved in the growth of abnormal new blood vessels (called choroidal neovascularization) in wet AMD. Two different drugs, Fovista and Rinucumab were proven ineffective.
Now that VEGF has been identified as an important target for wet AMD patients, it is likely that longer-lasting anti-VEGF drugs will be available within the next few years. In addition, new molecular targets involved in abnormal blood vessel growth are being identified through research supported by NIH, BrightFocus Foundation, and others. It is likely that blocking these, in addition to VEGF, will prove more effective and less burdensome than the current anti-VEGF treatments.
- Macular Degeneration Toolkit (Helpful Information to Understand and Manage Macular Degeneration)
- Expert Information on Macular Degeneration (Articles)
- BrightFocus Chats (Audio Presentations on Macular Degeneration)
- Treatments for Age-Related Macular Degeneration (Fact Sheet)
- Promising New Treatments for AMD (Audio and Transcript)
- Injections for Wet Macular Degeneration: What to Expect (Article)
- How Effective are Age-Related Macular Degeneration Treatments? (Article)
- Macular Degeneration: Essential Facts (Publication)
This content was last updated on: December 3, 2019
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