Some might say that we’re nearing consensus in the debate over the wisdom of using Avastin (bevacizumab, Genentech) off-label in patients who could otherwise be treated with the strikingly similar, but FDA approved, treatment Lucentis (ranibizumab, Genentech). The one-year results from the Comparison of AMD Treatments Trials (CATT) study revealed little difference in efficacy between Lucentis and Avastin.1 Does that mean there’s no valid reason to continue to encourage the use of a $2,000 per month treatment when a $50 treatment will do?2 A lesson in the history of anti-VEGFs reveals that there’s more to this decision than what can be gleaned by efficacy results alone.

In May 2005, Bascom Palmer retinal specialist, Philip J. Rosenfeld, M.D., Ph.D., had the idea to try something that no one else had dared. He was the first to ask a pharmacist to transfer Avastin from its glass vial into a syringe suitable for injection in the eye.3  Since so little Avastin was needed for ocular use compared to how much you need to pump into a cancer patient’s bloodstream, the price tag would be negligible.

Two months later, Dr. Rosenfeld stole the spotlight at the American Society of Retina Specialists meeting in Montreal by presenting his results.4 This was the same meeting where Genentech revealed its remarkable Lucentis data.5 From a PR standpoint, it was all downhill from there for Genentech. But, for patients, the increased publicity likely meant greater accessibility to a treatment that might otherwise be financially unattainable. Yet, the question remained, was it really safe?

Genentech was concerned. Avastin was manufactured for IV use, not for injection into the eye. For this, greater sterility controls are needed. Also, Avastin has to be diluted at the pharmacy to make intravitreal injection possible. Can patients and doctors rely on the controls and sterility of their local compounding pharmacies, where there are no formal inspections for dilution? The FDA actually issued a warning letter to one Massachusetts pharmacy that was repackaging Avastin, saying: “The moment a sterile container is opened and manipulated, a quality standard (sterility) is destroyed and previous studies supporting the standard are compromised and are no longer valid.” The agency expressed particular concern for risk of endophthalmitis.6 This, combined with an FDA inspection of Genentech’s own manufacturing facility led the company to announce, in 2007, that it would no longer allow for distribution of Avastin to compounding pharmacies.7

But the company was harshly criticized and many believed they were being driven by greed. A compromise was needed. It came in the form of the company’s agreement to sell Avastin to physicians who could then direct the drug to a compounding pharmacy.8 Meanwhile, in order to resolve the manufacturing concerns raised by the FDA, the company had to destroy more than $200 million worth of Avastin deemed unsuitable for use in the eye.9 The company notes that the destroyed product would have been entirely suitable for its approved use as an intravenous cancer medication.

As Diana L. Shechtman, O.D., and Paul M. Karpecki, O.D., report in this month’s “Research Review,” Avastin has now been proven to be just as effective as Lucentis in visual improvement when used for the treatment of wet AMD. Does that mean it’s the best choice? Which would you choose for your loved ones? The expensive one intended specifically for eyes, or the cheap one that’s been handled in a less rigorously controlled environment?

For additional commentary on this subject, see “What Motivated Lucentis Development?”

Amy Hellem

1. 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.
2. Klein RM, Klein RB. Avastin versus Lucentis: ethical issues in treatment of age-related macular degeneration. Retina 2007 Nov-Dec;27:1163-5.
3. Goldstein J. Two Drugs: How a Miami Doctor Found a Cheap Way to Save People’s Sight––and Got a Lesson in Medicine & Money. Miami Herald, November 14, 2006.
4. Rosenfeld PJ. Intravitreal avastin: the low cost alternative to lucentis? Am J Ophthalmol. 2006 July;142:141-3.
5. Peterson L. American Society of Retinal Specialists, Montreal, Canada, July 16-20, 2005. Trends-in-Medicine.
6. FDA Compounding Pharmacy Warning Letter. Available at: (accessed July 6, 2011).
7. Genentech Letter to Physicians. Available at: (accessed July 6, 2011).
8. Genentech Compromise Letter. Available at: (accessed July 6, 2011).
9. Genentech Open Letter. Available at: (accessed July 6, 2011).