Macular Degeneration Treatments (Investigational)
Investigational treatments for age-related macular degeneration (AMD) are therapies that are in various stages of development but have not yet been approved by the FDA for use in the United States, though they might be available in other countries.
In some cases, people in the U.S. can receive these treatments prior to FDA approval, especially if they are enrolled in a clinical trial that helps determine safety and effectiveness of the medication, surgery or other therapy.
Eylea and PDGFR-beta combination. In January 2014, Regeneron Pharmaceuticals and Bayer HealthCare announced an agreement to jointly develop an innovative antibody to the Platelet-Derived Growth Factor Receptor Beta (PDGFR-beta) as a potential combination therapy with Regeneron's FDA-approved Eylea (aflibercept) injections for the treatment of wet age-related macular degeneration (wet AMD).
According to the companies, preclinical data suggest that blocking PDGFR-beta as well as vascular endothelial growth (VEGF) can provide treatment advantages over inhibiting VEGF alone with Eylea or other FDA-approved treatments. Human clinical studies of the combination therapy are planned to begin in early 2014.
"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.
In 2012, two-year results of the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) sponsored by the National Eye Institute (NEI) to compare the effectiveness of Avastin and Lucentis (see news item) in the treatment of wet AMD, revealed Avastin was equivalent to Lucentis when used in similar dosing regimens. In all treatment groups in the study, at least 60 percent of patients attained visual acuity that met or exceeded the legal standard for driving vision (20/40 or better).
Some eye care practitioners choose to use Avastin off label for AMD treatment, because costs to patients may be significantly lower than when using 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.
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.
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.
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.
In April 2013, Oraya Therapeutics announced publication of the results of its INTREPID study evaluating the safety and efficacy of the company's Oraya Therapy Stereotactic Radiotherapy for the treatment of wet AMD. The study met primary endpoints, showing that a single dose of low-voltage X-rays delivered by the company's IRay Radiotherapy System significantly reduced the need for anti-VEGF injections, with a favorable safety profile one year after the procedure.
The non-invasive, one-time radiation treatment is applied with advanced robotics, a laser-guided positioning system, and a patented methodology for eye stabilization and tracking, according to the company. Oraya Therapy takes approximately 20 minutes, is performed in an outpatient setting, and no post-treatment recovery period is required before resuming normal activity, the company says.
The treatment was performed at 21 sites in five European countries, and a total of 230 patients with wet AMD enrolled in the study.
Results showed that patients who had previously been treated with anti-VEGF injections for up to three years needed 32 percent fewer injections after Oraya Therapy compared with a control group, and 25 percent of patients receiving the radiation therapy needed no further injections.
Oraya's IRay Radiotherapy System is a CE-marked medical device and the procedure currently is available to patients in the U.K. and Switzerland.
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.
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.
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 patients 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 August 2014]