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Macular Degeneration Treatments
(Investigational)

By Marilyn Haddrill; reviewed by Gary Heiting, OD

Investigational treatments for macular degeneration (AMD) are in various stages of research or FDA clinical studies.

This usually means that the drug or treatment is not generally available, unless you happen to be enrolled in a clinical trial that helps determine safety and effectiveness.

Investigational Treatments for Macular Degeneration

Avastin. Some eye doctors are using Avastin (bevacizumab), an FDA-approved cancer medication produced by Genentech, as an "off label" treatment for macular degeneration.

"Off label" use means that Avastin has not been specifically FDA-approved as a macular degeneration drug. While Genentech markets Avastin for treatment of colorectal cancer, the company has announced it has no plans to place the drug in clinical trials for treatment of macular degeneration.

When used off label to treat AMD, Avastin, like FDA-approved macular degeneration drugs Macugen (Eyetech) and Lucentis (Genentech), is injected directly into the vitreous in the back of the eye.

Recently, a study sponsored by the National Eye Institute (NEI) called the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) was initiated to assess the comparative effectiveness of Avastin and Lucentis for the treatment of AMD. First-year results published in May 2011 revealed the two drugs showed equal effectiveness (see news item). The CATT will continue through a second year of treatment to evaluate longer-term effects of the drugs on vision and safety.

Some eye care practitioners continue to use Avastin off label for AMD treatment, because costs to patients may be significantly lower than that of Lucentis (which received FDA approval as a macular degeneration treatment in 2006).

Some eye doctors argue that Lucentis should be the preferred treatment, even though it is more expensive, because the drug has undergone clinical trials with verifiable results specifically as a macular degeneration treatment.

iSONEP. Currently in early stage clinical trials, this novel treatment for "wet" AMD involves injections of a therapeutic antibody into the eye. Being developed by the biotechnology company Lpath, iSONEP (sphingomab) appears to target abnormal blood vessel growth in AMD as well as inflammation and excessive formation of fibrous tissue.

In December 2010, Lpath announced it had granted Pfizer a global license for commercial development and future sales of the drug pending appropriate studies and regulatory approvals.

The two companies currently are conducting a phase 2 study to evaluate the efficacy and safety of iSONEP with and without Lucentis/Avastin for the treatment of wet AMD. Results of the study are expected in early 2013.

Forsight VISION4 implant. In January 2012, Genentech announced it will make its first milestone payment to ForSight VISION4 as part of an exclusive license agreement to develop the company's investigational drug delivery device, designed to provide sustained delivery of Lucentis to the retina for the treatment of wet AMD.

The device is a refillable drug port delivery system (PDS) designed to release Lucentis over a period of months, eliminating the need for monthly intraocular injections. The milestone payment to ForSight VISION4 is based on Genentech's decision to submit an Investigational New Drug (IND) application to the FDA for clinical testing of the device in combination with Lucentis.

MC-1101. Early study results indicate that this investigational AMD drug applied to the eye's surface appears to increase blood flow in the retina, according to developers MacuCLEAR Inc. and Mystic Pharmaceuticals Inc. The VersiDoser drug delivery system used with the treatment delivers a "spray plume" in lieu of eye drops for effective penetration to the back of the eye.

"This study provides additional scientific evidence supporting our theory that restoring blood flow in the choroid will have a positive effect on preventing the progression of this terrible disease," said MacuCLEAR CEO and President Philip G. Ralston Jr.

Evizon. This investigational treatment for wet AMD has found new life, now that Ohr Pharmaceutical announced in late 2009 that it acquired the technology from Genaera. Known as squalamine, the drug has demonstrated ability to prevent development of abnormal blood vessels that damage the eye in wet AMD. Company officials say the drug's safety profile is a major advantage, and researchers are developing ways to enhance the drug's properties.

Zybrestat. In June 2010, Oxigene announced encouraging preclinical data regarding development of its investigational Zybrestat treatment for wet AMD. Unlike other macular degeneration drugs, Zybrestat is being designed for topical use in the form of eye drops and could eliminate the need for eye injections. The company said it believes the topical formulation could be ready for clinical development in early 2011.

In December 2011, the company presented encouraging data from a phase 2 study of Zybrestat for the treatment of polypoidal choroidal vasculopathy (PCV) — a potentially blinding eye disease that involves the growth of tiny, abnormal blood vessels under the retina. Oxigene's CEO said Zybrestat or a similar topical compound might one day become a "major breakthrough in treating retinal diseases," and that the company is seeking "a partner with strong expertise and experience in ophthalmic drug development to advance this promising clinical program."

Fenretinide. Based on positive study results, ReVision Therapeutics has announced that a late-stage (phase 3) clinical trial will be launched in 2011 for fenretinide as a treatment for dry macular degeneration. A demonstration of effectiveness and safety could lead to FDA approval.

Fenretinide, a derivative of vitamin A, has been shown to reduce growth of lesions associated with geographic atrophy — a condition associated with end-stage dry AMD. When geographic atrophy occurs, a lesion forms in the central part of the macula and causes significant central vision loss.

Study results presented at the 2010 American Academy of Ophthalmology (AAO) conference showed that fenretinide also appears to reduce the possibility of choroidal neovascularization — formation of abnormal blood vessels associated with advanced or "wet" macular degeneration.

Fenretinide is designed to be taken orally in pill form. Side effects can include delayed dark adaptation.

NT-501. In April 2011, Neurotech Pharmaceuticals announced promising results in a clinical study of its NT-501 intraocular implant for the treatment of retinitis pigmentosa.

The implant contains genetically modified human cells capable of secreting a nerve growth factor capable of rescuing and protecting dying photoreceptors in the retina. The company says the treatment might also be effective for the treatment of macular degeneration in the future.

Radiation treatment. Theragenics Corporation is working on a device called the TheraSight Ocular Brachytherapy System that uses low energy x-rays for treating AMD. Early clinical studies are being conducted to test the therapy's safety and feasibility in treating the abnormal blood vessel formation associated with wet AMD.

Another company, Oraya Therapeutics, announced in May 2011 that it has completed enrollment for a European study to evaluate radiation therapy for treating wet AMD. Participants will receive anti-VEGF injections in addition to radiation therapy, which will be evaluated for potential to enhance outcomes and reduce the need for costly injections.

Oraya's proprietary IRay radiotherapy system delivers robotically controlled low-energy X-rays to the eye in a one-time, non-surgical procedure that typically takes less than 15 minutes. The goal of the treatment is to reduce or eliminate the need for subsequent anti-VEGF injections. One-year results of the study are expected in the second quarter of 2012.

In February 2012, researchers reported disappointing results of a phase 3 multi-center study of a radiation therapy for wet AMD developed by NeoVista combined with anti-VEGF injections. Patients receiving the radiation treatment (called epimacular brachytherapy) and approximately six Lucentis injections over a period of 2 years lost visual acuity, while patients who received approximately 11 Lucentis injections without the radiation therapy exhibited a slight gain in vision.

Artificial retinas. Research increasingly has become focused on developing artificial retinas or methods of stimulating the retina for those who have experienced permanent vision loss from retinal disease. As an example, Optobionics is investigating the Artificial Silicon Retina (ASR) microchip as a way of stimulating healthy retinal cells to restore vision for those who have diseases such as retinitis pigmentosa and macular degeneration.

Gene therapy. Research into gene therapy as a potential treatment for macular degeneration is in early stages. But investigators are searching for ways to introduce specially encoded genes that could alter processes causing macular degeneration.

Stem cells. In what could be a milestone for treatment of dry AMD, Advanced Cell Technology (ACT) received approval in the U.S. and Europe in 2011 to begin clinical trials to investigate the safety and effectiveness of using retinal pigment epithelial (RPE) cells derived from human embryonic stem cells for the treatment of Stargardt's disease and dry macular degeneration.

Stargardt's disease (also called Stargardt's macular dystrophy) is a form of macular degeneration that affects young people. It affects an estimated 80,000 to 100,000 people in the U.S. and Europe, and causes progressive vision loss, usually starting between the ages of 10 to 20.

In January 2012, ACT announced the first patient in Europe received the treatment, and the following month the company announced three patient in the U.S. had been treated. Three trials will be conducted in the U.S. and Europe, with 12 patients enrolled in each trial. Preliminary results are expected in early 2013.

In February 2012, another company, StemCells Inc., announced it will begin FDA-approved phase 1/2 clinical trials to evaluate the safety and preliminary effectiveness of the company's purified human neural stem cell treatment for dry AMD.

The company plans to enroll 16 patients and the stem cells will be administered by a single injection into the space beneath the retina. Patients will be examined at predetermined intervals over 1 year and then will be followed for an additional 4 years in a separate observational study.

Please click here to read about FDA-approved macular degeneration treatments.

[Page updated February 2012]