Genentech Restricts Sales of Less Costly Agent for Macular Degeneration Treatment

SAN FRANCISCO, Oct. 12 -- Retinal specialists who use Genentech's bevacizumab (Avastin) off-label, instead of ranibizumab (Lucentis), to treat macular degeneration will soon find that their sources for the drug have dried up.

In a letter to physicians, Genentech has announced that as of Nov. 30 it will stop supplying bevacizumab, the antiangiogenic monoclonal antibody, to compounding pharmacies, because of safety concerns that the drug is being used for an unapproved indication.

The company also makes ranibizumab, an agent similar to bevacizumab. Ranibizumab, which is indicated for ocular conditions, is priced at about ,000 per injection, compared with about for bevacizumab syringes as prepared by compounding pharmacies.

The drugs are both humanized monoclonal antibodies derived from a mouse monoclonal antibody, and both bind to and inhibit all the biologically active forms of VEGF-A. But the bevacizumab molecule is about three times larger than that of ranibizumab. The latter agent is specially formulated for intravitreal use, whereas the latter is designed for intravenous infusion.

Bevacizumab is approved only as an IV infusion for treatment of metastatic colorectal cancer and non-small-cell lung cancer. But, said Philip J. Rosenfeld, M.D., Ph.D., of the Bascom Palmer Eye Institute in Miami, it has been extensively used off-label in intravitreal injections to retard or prevent neovascularization in retinal disorders such as age-related macular degeneration.

Genentech will still sell bevacizumab to hospital pharmacies and individual physicians, but retinal specialists in private practice may have difficulty getting supplies of the drug.

And while Medicare pays 80% of the costs of ranibizumab, many secondary insurers won't pick up the difference, leaving some patients, who may need up to six injections a year, unable to afford a potentially beneficial therapy, said Dr. Rosenfeld.

"Avastin provides not only a drug that can be used in patients who can't afford Lucentis, but many doctors feel as if they don't want to subject themselves or their patients to the economic risks of Lucentis," said Dr. Rosenfeld, who pioneered the used of bevacizumab for neovascular diseases of the posterior segment of the eye.

He and his colleagues have had extensive experience with bevacizumab in the treatment of macular degeneration and other ocular diseases in which the drugs target, vascular endothelial growth factor (VEGF) plays a pathogenic role.

In July 2005 they published encouraging results with the drug in two patients, one with neovascular macular degeneration in her one good eye despite the best available therapy, and the other in a patient with a central retinal vein occlusion.

Dr. Rosenfeld said in an interview that he has used ranibizumab in many of his patients since it became available in 2006, but noted that in recent months many of those patients have been switched back to bevacizumab.

"For those patients that need treatment every two to three months, our general impression is that there's no difference the two drugs, and when we reviewed our data retrospectively, that was confirmed," he said. "A few patients did better with Lucentis and a few did better with Avastin, but for the vast majority of patients there is no difference between the two drugs."

He noted that a definitive answer to the question of therapeutic equivalency of the drugs won't be available until the conclusion of a head-to-head trial of the drugs sponsored by the National Eye Institute. Enrollment for that trial is scheduled to begin at the end of the year.

In an article in the Oct. 5, 2006 issue of the New England Journal of Medicine, Genentech's chief medical officer Hal Barron, M.D., said that the company has "a huge database suggesting that Lucentis is very effective and very safe, so we are just not sure of the value of taking something that is not formulated for the eye and subjecting patients to a randomized trial when there is, in our opinion, a very low likelihood of its being superior."