Researchers are reporting results from the first year of a two-year clinical trial that Avastin, a drug approved to treat some cancers and that is commonly used off-label to treat age-related macular degeneration (AMD), is as effective as the Food and Drug Administration-approved drug Lucentis for the treatment of AMD.
The report, from the Comparison of AMD Treatments Trials (CATT), was published online April 28 in the New England Journal of Medicine. The clinical trial is funded by the National Eye Institute (NEI), a part of the National Institutes of Health.
The University of Iowa Hospitals and Clinics was one of 43 clinical centers in the United States to participate in the CATT study.
This study showed that Lucentis and the much less expensive Avastin were equal for treating neovascular Age-Related Macular Degeneration," said James Folk, MD, UI professor of ophthalmology and visual sciences and principal investigator for CATT at the UI. "The results give doctors and their patients more treatment options for AMD including which drug to use and when to inject it."
AMD is the leading cause of vision loss and blindness in older Americans. In its advanced stages, the wet form of AMD spurs the growth of abnormal blood vessels, which leak fluid and blood into the macula and obscure vision. The macula is the central portion of the retina that allows us to look straight ahead and to perceive fine visual detail. Accumulation of fluid and blood damages the macula, causing loss of central vision. AMD can severely impede mobility and independence. Many patients are unable to drive, read, recognize faces or perform tasks that require hand-eye coordination.
The biotechnology company Genentech manufactures both Lucentis and Avastin. Lucentis has been approved by the U.S. Food and Drug Administration (FDA) for treatment of the wet form of AMD. Avastin has been approved by the FDA for treating certain types of cancer. Because of its similarity to Lucentis and its availability, eye doctors have also used Avastin "off-label" to treat wet AMD.
NEI launched CATT in 2008 to compare Lucentis and Avastin for treatment of wet AMD. The study has now reported results for 1,185 patients treated at 43 clinical centers in the United States.
Patients were randomly assigned and treated with one of four regimens for a year. They received Lucentis monthly or as needed (pro re nata, PNR), or Avastin monthly or PRN. Enrollment criteria required that study participants had active disease.
Patients in the monthly dosing groups received an initial treatment and then had an injection every 28 days. Patients in the PRN groups received an initial treatment and were then examined every 28 days to determine medical need for additional treatment. PRN groups received subsequent treatment when there were signs of disease activity, such as fluid in the retina. Ophthalmologists involved in patient care did not know which study drug a patient was getting.
Change in visual acuity served as the primary outcome measure for CATT. Thus far, visual acuity improvement was virtually identical (within one letter difference on an eye chart) for either drug when given monthly. In addition, no difference was found in the percentage of patients who had an important gain or loss in visual function. Also, when each drug was given on a PRN schedule, there was no difference (within one letter) between drugs. PRN dosing required four to five fewer injections per year than monthly treatment. Visual gains were about two letters less with PRN than with monthly treatment but overall visual results were still excellent.
Serious adverse events (primarily hospitalizations) occurred at a 24 percent rate for patients receiving Avastin and a 19 percent rate for patients receiving Lucentis. These events were distributed across many different conditions, most of which were not associated with Avastin in cancer clinical trials where the drug was administered at 500 times the dose used for AMD. The number of deaths, heart attacks and strokes were low and similar for both drugs during the study. CATT was not capable of determining whether there is an association between a particular adverse event and treatment. Differences in serious adverse event rates require further study.
Investigators in the CATT study will continue to follow patients through a second year of treatment. These additional data will provide information on longer-term effects of the drugs on vision and safety.
The FDA has not evaluated data from the CATT trial.
Find more information about this clinical trial (NCT00593450) at http://www.clinicaltrials.gov.