Avastin and Lucentis for Macular Degeneration: Head-to-Head Once Again

Photograph of a retina with wet age-related macular degeneration

Year Two results from the Comparison of Age-Related Macular Degeneration (AMD) Treatments Trials (CATT) that evaluated the effectiveness of Avastin (bevacizumab) versus Lucentis (ranibizumab) in a head-to-head clinical trial are now available. CATT is a multi-center, prospective clinical trial, funded by the National Eye Institute (NEI), a component agency of the National Institutes of Health.

About Age-Related Macular Degeneration (AMD)

In wet macular degeneration, the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal blood vessels that develop into a cluster under the macula (called choroidal neovascularization).

The macula is the part of the retina that provides the clearest central vision. Because these new blood vessels are abnormal, they tend to break, bleed, and leak fluid under the macula, causing it to lift up and pull away from its base. This damages the fragile photoreceptor cells, which sense and receive light, resulting in a rapid and severe loss of central vision.

Anti-Angiogenic Drugs

Angiogenesis is a term used to describe the growth of new blood vessels and plays a crucial role in the normal development of body organs and tissue. Sometimes, however, excessive and abnormal blood vessel development can occur in diseases such as cancer (tumor growth) and AMD (retinal and macular bleeding).

Substances that stop the growth of these excessive blood vessels are called anti-angiogenic (anti=against; angio=vessel; genic=development), and anti-neovascular (anti=against; neo=new; vascular=blood vessels).

The focus of current anti-angiogenic drug treatments for wet AMD is to reduce the level of a particular protein (vascular endothelial growth factor, or VEGF) that stimulates abnormal blood vessel growth in the retina and macula; thus, these drugs are classified as anti-VEGF treatments. At present, these drugs are administered by injection directly into the eye after the surface has been numbed.


Avastin is an anti-VEGF drug that is FDA-approved since 2004 for intravenous use in colorectal cancer. It is currently used on an “off-label” basis (i.e., via eye injection) to treat wet AMD. The cost per treatment with Avastin is approximately $50.


Lucentis was derived from a protein similar to Avastin, specifically for injection in the eye to block blood vessel growth in AMD. In 2005, clinical trials established Lucentis as highly effective for the treatment of wet AMD. The FDA approved Lucentis in 2006. The cost per treatment with Lucentis is approximately $1,200-$2,000.

Please note: The CATT study tested both monthly dosing, used in Lucentis trials, and dosing “as needed” (called “pro re nata,” or PRN), used in Avastin treatment for AMD.

2011: Year One CATT Study Results

The first-year results of the two-year study were published in the May 19, 2011 issue of the New England Journal of Medicine. Initial reports indicated that Avastin was as effective as Lucentis for the treatment of AMD. From Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration: The CATT Research Group:

In the randomized Comparison of Age-Related Macular Degeneration Treatments Trials (CATT), we set out to assess the relative efficacy and safety of [Lucentis] and [Avastin] and to determine whether an as-needed regimen would compromise long-term visual acuity, as compared with a monthly regimen.

The CATT study revealed equal effectiveness of both Lucentis and Avastin in the management of AMD at one year. The two drugs had equivalent effects on visual acuity at all time points throughout the first year. A monthly dosing schedule with either drug yielded greater visual gains than PRN (as needed), but the PRN schedule still gave patients substantially improved vision. Lucentis led to a greater reduction in fluid under the retina, requiring slightly fewer PRN injections.

2012: Year Two CATT Study Results

The second-year and final results of the two-year study, published online on May 2, 2012 and in the July 2012 issue of the journal Ophthalmology, confirm that Avastin is as effective as Lucentis for the treatment of wet AMD. From Ranibizumab and Bevacizumab for Treatment of Neovascular Age-Related Macular Degeneration: Two-Year Results:

At both 1 and 2 years, [Avastin] and [Lucentis] had similar effects on visual acuity when the dosing regimen was the same… Small differences in mean gain in visual acuity emerged between dosing regimens.

The magnitude and durability of the therapeutic effect … is remarkable when one considers the natural history of neovascular AMD and the modest efficacy of treatments before [Avastin] and [Lucentis]. At two years, 60% or more of the patients in all groups had 20/40 vision or better, which was dramatically better than among patients who were untreated.

Nevertheless, the study authors sounded a clear cautionary note about Avastin:

Over two years, the rates of death, [heart attack], and stroke did not differ between drugs. The higher rate of serious adverse events for [Avastin]-treated patients reported in year 1 remained in year 2… Although the number of events is small, this has been an area of concern in previous studies of [Avastin]… Results from ongoing randomized clinical trials worldwide may provide additional, independent information about the risk of treatment with [Avastin] relative to [Lucentis].

A Final Word from the National Eye Institute

From an NEI press release, entitled Avastin and Lucentis are equivalent in treating age-related macular degeneration:

At two years, Avastin and Lucentis, two widely used drugs to treat age-related macular degeneration (AMD), improve vision when administered monthly or on an as-needed basis, although greater improvements in vision were seen with monthly administration.

“Both drugs were highly effective regardless of the approach to dosing. There was slightly less vision gain with as-needed treatment. Patients seeking the small extra advantage of monthly treatment need to be mindful of the additional burden, risks, and costs of monthly injections. Since as-needed dosing required 10 fewer eye injections over the course of two years and yielded similar visual results, many patients may choose this option,” said Daniel F. Martin, M.D., study chair for CATT and chairman of the Cole Eye Institute at the Cleveland Clinic.

VisionAware will continue to report on clinical trials and research related to Avastin and Lucentis.