Avastin (bevacizumab, Genentech) is a full-length, humanized, monoclonal antibody that is FDA approved for the systemic treatment of certain cancers. Tumors need blood to grow and Avastin, when administered intravenously, halts new blood vessel growth. It can also cause serious side effects because IV administration means it travels throughout the entire bloodstream.

Lucentis (ranibizumab, Genentech), on the other hand, is an antigen-binding fragment. It is a smaller molecule that was specifically developed and approved to treat eye diseases. To understand exactly what that means requires a little history.

Antibodies are big molecules, which is fine if you intend to inject them into the blood stream. But, if your intention is to administer them directly into the eye and want them to travel all the way to the retina, you might hit a few roadblocks—at least that’s what Genentech scientists thought when they decided to create this second anti-VEGF drug.¹

Using radioactive material, Genentech compared how well full-length antibodies traveled in monkey eyes versus how well fragments of the antibodies traveled and found that the smaller ones could move more easily through the eye.¹ This would seem to support the need for developing Lucentis. It would also imply that Lucentis should be more effective. But, we now see that’s not the case. As Diana L. Shechtman, O.D., and Paul M. Karpecki, O.D., report in this month’s Research Review, Avastin has been shown to be just as effective as Lucentis in visual improvement when used for the treatment of wet AMD.² How can this be?

For starters, when Genentech compared how well a full-length molecule travels, they used a different antibody that was about the same size, but was easier to track in monkey eyes. “This may have been a mistake,” says University of Wisconsin scientist Wendy Bedale, Ph.D.³ Whether or not the substitution was part of an intentional scheme on behalf of Genentech to get more bang for their research buck, as skeptics claim, we’ll never really know; but it seems improbable based on the events that followed—many of which cast the company in a very unflattering light and ate into a substantial chunk of its profits.

For more on this subject, see "Efficacy Aside."

1. Mordenti J, Cuthbertson RA, Ferrara N, et al. Comparisons of the intraocular tissue distribution, pharmacokinetics, and safety of 125I-labeled full-length and Fab antibodies in rhesus monkeys following intravitreal administration. Toxicol Pathol 1999. 27:536-44.
2. Martin DF, Maguire MG, Ying GS, et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011 May 19;364(20):1897-908.
3. Avastin/Lucentis Update 41: The Story Behind the Invention of Avastin and Lucentis. Available at: http://irvaronsjournal.blogspot.com/2010/06/avastinlucentis-update-41-story-behind.html. (accessed July 6, 2011).