By Kevin E. Noonan —

Responding to outrage, protest, and threats of political and legal action, or perhaps just belatedly recognizing that it was in the middle of a public relations nightmare, Genentech last week announced that it would delay until the end of the year implementation of its decision to "no longer allow compounding pharmacies to purchase Avastin® directly from drug wholesalers," a ban that was originally set to begin on November 30, 2007.

Genentech’s decision is related to the use of the company’s anticancer drug, Avastin® (bevacizumab, a monoclonal antibody), for neovascular or "wet" age-related macular degeneration (AMD), a condition that if untreated leads inexorably to blindness.  This is an off-label use; another Genentech drug, Lucentis® (ranibizumab injection), has been approved for AMD treatment.  The choice of the off-label use is related to the cost differential between the drugs:  Avastin® treatment costs from $20-60 per dose, while Lucentis® treatments cost $2,000/dose.  Since neither drug is a cure for AMD, patients require maintenance doses substantially for the remainder of their lives.  The cost differential is due to both differences in cost (Avastin® is priced at only $600/vial) and because the drug is injected into the eye at such small doses (0.1cc) that each vial of Avastin® can deliver 30 doses ($20/dose).

Genentech’s announcement was based, at least in part, on FDA concerns over sterility and packaging of the reformulated Avastin®, and concerns that Avastin® had not been "designed, manufactured or approved" for the off-label use (see "Genentech Acts to Halt Off-label Use of Avastin® for Age-related Macular Degeneration").  It is apparent that Genentech management feels justified in charging more for Lucentis® due to the company’s extensive testing and regulatory efforts (and costs) to establish safety and efficacy of the drug for AMD (see "Genentech CEO Defends Differential Cost for Avastin®/Lucentis® Treatment of Macular Degeneration").

The retinal community responded negatively to the news that Genentech planned to cut off the source of Avastin® to formulating pharmacies, which provided a safe and reliable source of the reformulated drug.  In particular, the American Society of Retinal Specialists (ASRS) organized their members, sending them information regarding the effects of the ban, and protested Genentech’s actions to the company, in letters threatening that the organization was "actively investigating the legality, cost, and ramifications of options open to its membership to keep Avastin available to our patients . . . in conjunction with the American Association of Ophthalmologists and other groups."  Importantly, ASRS reminded its members that Avastin® was expected to remain available until next spring and from hospital pharmacies even after the ban is put into place.

Now, in news provided by Dr. Edward Chaum (at left), Plough Foundation Professor of Ophthalmology, University of Tennessee, Genentech and ASRS had a conciliatory meeting with very positive results that were reported to the membership in an e-mail update.  First, Genentech has delayed its proposed ban until January 1, 2008, and consequently Avastin® is expected to be available until at least next summer.  Also, the ASRS representatives meeting with Genentech company officials, including Genentech CEO Dr. Arthur Levinson (at right), had a better understanding of the circumstance
surrounding the decision to ban sales to formulating pharmacies.  These included an incident with an FDA inspector that resulted in the company destroying four lots of Avastin®, corresponding to 382,000 vials (or almost 10 million AMD doses) at a cost of more than $200 million.  The ASRS update stated that "there was indeed reason for Genentech to consider the continuation of sales to compounding pharmacies a potential serious liability for the company, and that a reasonable business person might have come to the same decision about limiting sales."

As a consequence, the "bad guy" role has been shifted to the FDA.  The ASRS reports that Senator Herb Kohl (D-WI) of the Senate Special Committee on Aging scheduled a teleconference with FDA representatives and members of the American Association of Ophthalmologists (AAO).  Genentech has agreed that "if the FDA will no longer raise issues with them about providing Avastin to compounding pharmacies, they will lift the embargo on sales to these pharmacies."

The update ends on a positive note:

In summary, our recommendation to the ASRS membership is that we go forward in good faith and with appropriate caution, and continue our efforts to marshal the resources of the medical, regulatory, and pharmaceutical industries to ensure that our patients maintain access to the treatments they need.  This is not to say that we will always agree with industry and the FDA — we serve different masters, and our missions, while similar, are not always exactly aligned.  Physicians have no responsibility to stockholders, nor does the FDA govern our relationship with our patients.  But perhaps we can agree to be open-minded, and to communicate.

For additional information on this topic, please see:

• "Genentech Acts to Halt Off-label Use of Avastin® for Age-related Macular Degeneration," October 21, 2007
• "Genentech CEO Defends Differential Cost for Avastin®/Lucentis® Treatment of Macular Degeneration," June 6, 2007
• "Retinal Specialist on the Avastin®/Lucentis® Controversy," February 23, 2007
• "Lower Doses of Genentech’s Avastin® Effective in Treating Lung Cancer," February 23, 2007