Duke is a site for this long-anticipated, multicenter clinical trial, which will compare the effectiveness of Lucentis and Avastin in treating this blinding eye disease.

In the battle to treat advanced age-related macular degeneration, there are currently two main contenders: Lucentis (ranibizumab) and Avastin (bevacizumab).

While Lucentis has demonstrated positive outcomes in patients through several well-controlled clinical trials, Avastin has been used only as an off-label drug. Since finding that off-label Avastin may actually benefit patients with neovascular AMD, its use has been extensive, and in many circles, its use has surpassed that of Lucentis. However, it is the price differential that really is noteworthy.

Until now, no one had compared the two directly. Now thanks to a long-anticipated multicenter clinical trial funded by the National Eye Institute, Lucentis and Avastin are going head-to-head in a study that will compare the relative safety and effectiveness of the two drugs.

Age-related macular degeneration (AMD), the leading cause of blindness in older Americans, is a disease that damages the macula, the area of the retina responsible for central vision. Nearly two million Americans are visually impaired by AMD, while more than seven million are at an increased risk of vision loss from the disease.

The wet form of AMD occurs when abnormal blood vessels start to grow under the retina. These new blood vessels can leak blood and fluid, damaging the macula and causing a rapid loss of vision. Both Lucentis and Avastin, which have similar chemical make-ups and are designed to inhibit a protein needed in blood vessel formation, are injected into the eye to treat wet AMD.

In February the National Eye Institute (NEI) announced the start of the “Comparison of AMD Treatments Trials” (CATT) study, which will be conducted at 47 clinical centers across the country to evaluate the relative effectiveness and safety of Avastin and Lucentis and determine if the treatment burden for patients can be reduced without compromising effectiveness. Duke Eye Center is one of these study sites.

Karl Csaky, MD, PhD, former associate professor of ophthalmology on the Duke Eye Center’s retina faculty and director of the Ophthalmic Clinical Trials Unit at the Duke Clinical Research Institute, was on the NEI’s planning committee for this trial and has been involved with the CATT study from the outset.

“This trial is unique in that it is really driven by a financial outcome,” he says. “We already have many studies showing that Lucentis can effectively treat wet AMD, but each dose of Lucentis costs more than 40 times as much as a dose of Avastin. From a practical perspective, it’s important to compare the outcomes from each drug because if Avastin works just as well as Lucentis, that could mean billions of dollars in cost savings for both patients and government health care programs like Medicare and Medicaid.”

The study will also provide new information on the value of customizing the delivery of these medications, Csaky adds. “We’ll be testing delivery of these drugs on both fixed (monthly) and variable (as needed) schedules in different groups of subjects. If it turns out that we can get just as good results on a variable regimen, that would be another form of cost savings.”

Lucentis was approved by the U.S. Food and Drug Administration (FDA) in June 2006 specifically for the treatment of wet AMD. The approval was based on evidence from clinical trials showing that Lucentis can improve vision in patients with wet AMD

“Approximately one-third of patients treated in these trials had a dramatic improvement in vision,” says Csaky. The down side: Lucentis currently costs around $2,600 per injection. Avastin was approved by the FDA in 2004 as an intravenous treatment for patients with advanced colorectal cancer and has been available for what is called “off-label” use for other health conditions. Around the United States and the world, it has been used off-label to treat wet AMD, with compounding pharmacies taking the large vials used for chemotherapy and packaging them into much smaller doses to inject into the eye.

Avastin is thought to remain in the eye longer than Lucentis, and therefore, possibly allowing for less frequent injections. Avastin is priced per vial for cancer use and repackaged into very small doses for AMD; it costs about $60 per injection, a fraction of the cost of Lucentis.

Lucentis and Avastin are both manufactured by Genentech Inc., which is not participating in the trial.

CATT will determine the relative safety and effectiveness of treating wet AMD in 1,200 patients throughout the country who will be divided randomly into four groups. Each group will receive a year’s worth of treatment with intraocular injections of either Lucentis or Avastin on a fixed (every four weeks) or variable schedule, provided as needed based on lesion activity. After one year, patients who were on a fixed schedule will receive additional treatment on either a fixed or varying schedule.

The study will measure changes in vision after treatment with each drug, as well as the number of treatments, anatomical changes in the retina, adverse events, and costs. Results are expected in 2011.

Now Enrolling at Duke

Duke vitreoretinal specialist Srilaxmi Bearelly, MD, MHS, former assistant professor of ophthalmology and the principal investigator for the Duke site of the CATT study, says that the Eye Center is now enrolling qualified patients for the study. Eligible patients must have wet AMD, have vision between 20/25 and 20/320, be at least 50 years of age, and have had no previous treatment for wet AMD in the study eye.

“Since these two drugs became available, this study has been in the making,” says Bearelly. “Ultimately we hope that the results will improve our treatment of wet macular degeneration. Potentially, we’ll b eable to reduce the frequency of treatments without compromising effectiveness, and therefore, reduce both the cost and treatment burden for our patients.”

While the trial is taking place, Lucentis and Avastin are still available to patients not enrolled in the study, Csaky says. “We are excited that the Duke Eye Center is a part of this unique clinical trial that is about science and about how we as a country can curtail health care costs while maintaining excellence in patient outcomes. We hope our patients will view participating in this trial as an opportunity to contribute to the practice of medicine and to the care and outcomes of those who will face AMD in the future.”

Subinvestigators are Brooks McCuen, MD, Sharon Fekrat, MD, and Ivan Suñer, MD. For more information about enrolling in this trial, contact Joyce Bryant at 919-684-0864.