July 25, 2006
(ATLANTA) Emory Eye Center retina specialists participated in clinical trials that have concluded that a new drug holds hope in the treatment of age-related macular degeneration (AMD). Clinical trials here at Emory and throughout the country have lead to U.S. Food and Drug Administration (FDA) approval of Lucentis™ (ranbizumab injection), a new intravitreal drug that treats the “wet” type of macular degeneration. The drug is made by Genentech.
Macular degeneration affects approximately 155,000 new Americans each year, with some 15 million people currently affected by it. In Georgia alone, some 35,000 people have the advanced form of AMD. For those over 60, it is the single largest cause of severe vision loss. According to the FDA, Lucentis ™ is the first treatment, when taken in monthly doses that can maintain the vision of more than 90% of newly-diagnosed patients with wet AMD.
The approval was based on evidence from past clinical trials showing that Lucentis ™ (ranibizumab) slows the progression of vision loss from advanced (“wet”) AMD. Approximately one-third of patients in the trials had improved vision at 12 months. Baker Hubbard, MD, a retina specialist at Emory Eye Center and principal investigator of the most recent trial at Emory evaluating Lucentis™, says “Central vision loss resulting from wet AMD can have a significant impact on someone’s life. With this drug we now have a treatment option with the potential to significantly improve vision for more than one-third of patients with newly-diagnosed wet AMD.”
Lucentis ™ is designed to inhibit the formation and leakage of new blood vessels in the eye that can lead to wet AMD disease progression and central vision loss. Wet AMD affects the macula, the portion of the eye responsible for the fine, detailed central vision required for everyday activities such as reading, driving and recognizing faces. It occurs when blood vessels at the back of the eye grow and leak blood and fluid, causing damage to the macula. Symptoms include blurred, gray or blank spots in the center of the visual field and distortion that makes edges or lines appear wavy.
The National Eye Institute (NEI) of the National Institutes of Health (NIH) has funded nearly $95 million and sponsored more than 300 research studies investigating neovascularization, or angiogenesis--the growth of new blood vessels in the eye.
When researchers found that a protein--vascular endothelial growth factor (VEGF)--was indicated in the growth of new blood vessels in such diseases as AMD, pharmaceutical companies began developing anti-VEGF therapies. Among those approved for treatment are Macugen, and now Lucentis.
The FDA approval of Lucentis is based on data from two large Phase III clinical trials (MARINA and ANCHOR). In these studies:
- Nearly all patients (approximately 95 percent) treated with Lucentis maintained vision and up to 40 percent improved vision at one year, as measured on the Early Treatment of Diabetic Retinopathy (ETDRS) eye chart.
- On average, patients treated with Lucentis in the MARINA study experienced an improvement of vision at two years compared to a loss of vision in the control group. In the ANCHOR study, patients treated with Lucentis on average experienced a gain in vision at one year compared to a loss of vision in the control group.
- Up to 40 percent of patients treated with Lucentis achieved vision of 20/40 or better.
In addition to data from the two pivotal studies, data from the Phase I/II FOCUS and Phase IIIb PIER studies were included in the FDA submission.
In clinical trials, the most common adverse reactions among patients treated with Lucentis (reported in at least 6 percent more patients than in the control groups in at least one study) included conjunctival hemorrhage, eye pain, vitreous floaters, increased intraocular pressure and intraocular inflammation. Although there was a low rate (less than 4 percent) of arterial thromboembolic events observed in the Lucentis clinical trials, there was no significant difference between the Lucentis and control groups, although there is a theoretical risk of these events with use of Lucentis. Serious adverse events related to the injection procedure occurred in less than 0.1 percent of intravitreal injections, including endophthalmitis, retinal detachments and traumatic cataracts. Other serious ocular adverse events observed among Lucentis-treated patients (occurring in less than 2 percent of patients) included intraocular inflammation and increased intraocular pressure. Lucentis is contraindicated in patients with hypersensitivity and ocular or periocular infections.
Prior to the formulation of Lucentis, Avastin, a drug used to treat colorectal cancer, had been coincidentally found to help those patients who also had advanced AMD. Avastin's chemical make-up is very similar to Lucentis, and ophthalmologists have used Avastin in past years to treat those patients.
AGE-RELATED MACULAR DEGENERATION
AMD is a common eye disease associated with aging that gradually destroys sharp, central vision. Central vision is needed for seeing objects clearly and for common daily tasks such as reading and driving. In some people, AMD advances so slowly that it will have little effect on their vision as they age. But in others, the disease progresses faster and may lead to a loss of vision in one or both eyes.
HOW AMD DAMAGES VISION
The retina is a paper-thin tissue that lines the back of the eye and sends visual signals to the brain. In the middle of the retina is a tiny area called the macula. The macula is made up of millions of light-sensing cells that help to produce central vision.
AMD occurs in two forms:
• Dry AMD--Ninety percent of all people with AMD have this type. Scientists are still not sure what causes dry AMD. Studies suggest that an area of the retina becomes diseased, leading to the slow breakdown of the light-sensing cells in the macula and a gradual loss of central vision.
• Wet AMD--Although only 10 percent of all people with AMD have this type, it accounts for 90 percent of all blindness from the disease. As dry AMD worsens, new blood vessels may begin to grow and cause "wet" AMD. Because these new blood vessels tend to be very fragile, they will often leak blood and fluid under the macula. This causes rapid damage to the macula that can lead to the loss of central vision in a short period of time.
The greatest risk factor is age. Although AMD may occur during middle age, studies show that people over age 60 are clearly at greater risk than other age groups. For instance, a large study found that people in middle-age have about a 2 percent risk of getting AMD, but this risk increased to nearly 30 percent in those over age 75.
Other AMD risk factors include:
Gender--Women tend to be at greater risk for AMD than men.
Race--Whites are much more likely to lose vision from AMD than Blacks.
Smoking--Smoking may increase the risk of AMD.
Family History--Those with immediate family members who have AMD are at a higher risk of developing the disease.
Both dry and wet AMD cause no pain. The most common early sign of dry AMD is blurred vision. As fewer cells in the macula are able to function, people will see details less clearly in front of them, such as faces or words in a book. Often this blurred vision will go away in brighter light. If the loss of these light--sensing cells becomes great, people may see a small--but growing--blind spot in the middle of their field of vision.
The classic early symptom of wet AMD is that straight lines appear crooked. This results when fluid from the leaking blood vessels gathers and lifts the macula, distorting vision. A small blind spot may also appear in wet AMD, resulting in loss of one's central vision.
Your eye care professional may suspect AMD if you are over age 60 and have had recent changes in your central vision. To look for signs of the disease, he or she will use eye drops to dilate, or enlarge, your pupils. Dilating the pupils allows your eye care professional to view the back of the eye better.
You may also be asked to view an Amsler grid, a pattern that looks like a checkerboard. Early changes in your central vision will cause the grid to appear distorted, a sign of AMD.
No treatment now exists for dry AMD. It has been suggested that taking certain extra vitamins and minerals may slow the progress of the disease. But this treatment needs much more research before scientists can know for sure if it's helpful.
Eye care professionals can treat some cases of wet AMD with laser surgery. This treatment involves aiming a strong light beam onto the new blood vessels to destroy them. Laser surgery is done in a doctor's office or in an eye clinic and lasts a short period of time. Although a person may go home the same day, he or she will need to return for follow-up exams.
The National Eye Institute is funding a number of research studies to learn what causes AMD and how it can be better treated. For instance, in the Age-Related Eye Diseases Study (AREDS), researchers are assessing the aging process in the eyes of thousands of older people to discover the earliest signs of AMD. The same study is also evaluating the effects of certain vitamins and minerals in preventing or slowing the progress of AMD.
At the same time, other scientists are trying to learn more about how the cells in the retina work. This knowledge will allow them some day to pinpoint the cause of the disease and design methods to prevent it.
WHAT CAN YOU DO?
Although there is no effective treatment for dry AMD at this time, it is crucial that those who progress to wet AMD and need laser surgery have it before the disease destroys central vision. For this reason, if you have dry AMD or are age 60 or older, you should have your eyes examined through dilated pupils at least once a year. You may also want to get an Amsler grid from your eye care professional to check your vision at home.
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Media Contact: Joy H. Bell
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