Comparison of Avastin versus Lucentis for treatment of wet type of Age-Related Macular Degeneration Treatments (CATT trial)

People with vascular diseases of the retina, such as age-related macular degeneration (AMD), diabetic macular edema, vascular occlusions like the central retinal vein occlusion, even retinopathy of prematurity (ROP) have been offered treatment in the form of injections of Ranibizumab (trade name Lucentis)or Bevacizumab (trade name Avastin) into the eye every few weeks. These injections control the expression of vascular endothelial growth factor (VEGF), which is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate. VEGF's normal function is to create new blood vessels during embryonic development, new blood vessels after injury, muscle following exercise, and new vessels (collateral circulation) to bypass blocked vessels. When VEGF is overexpressed, it can contribute to disease.

Genentech, a wholly owned susdiary of the Swiss pharmaceutical conglomerate Hoffmann-La Roche [], developed Lucentis, which is a monoclonal antibody fragment (Fab) derived from the same parent murine antibody as Avastin. It is much smaller than the parent molecule, and has a stronger binding to VEGF-A. This feature gives it anti-angiogenic properties, which has helped it get regulatory approval in many countries around the world to treat wet AMD, which is a common form of age-related vision loss. It is marketed in the United States by Genentech and elsewhere by Novartis. Avastin, developed specifically for use in colorectal cancers, was found to be useful in the eye for AMD as well. With a significant cost difference between Avastin at an average cost of $42 a dose (in the U.S.) versus Lucentis at an average cost of $1,593 a dose, there was a difference of opinion between retina specialists and those who marketed the drug, with the specialists claiming that the effect from both appeared to be equal, while the latter claimed they were not responsible for any untoward side-effects from the use of off-lable Avastin in the eye.

With an on-going debate that showed no signs of resolution, a clinical trial comparing the two treatments in patients with wet AMD (CATT) was planned to effectively answer the question whether Lucentis has any potential benefit over Avastin.

In a multicenter, single-blind, noninferiority trial, 1208 patients with neovascular (or wet) AMD were randomly assigned to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart.

The study group recently reported its result in the New England Journal of Medicine, with the conclusion that Avastin administered monthly or as needed was equivalent to Lucentis administered monthly or as needed respectively. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 μm) than in the other groups (152 to 168 μm, p = 0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (p>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with Avastin than with Lucentis (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66).

So the major conclusion from this CATT study is that at the end of 1 year, Avastin and Lucentis had equivalent effects on visual acuity when administered according to the same schedule. The authors mention that the differences in rates of serious adverse events require further study. (The study was funded by the National Eye Institute; ClinicalTrials.gov number, NCT00593450.)

p.s. In this continuing saga of Lucentis versus Avastin, New York Times reports that Genentech has been  offering secret rebates to eye doctors as an apparent inducement to get them to use more of the company’s expensive drug Lucentis rather than a less costly alternative.