Genentech Beset with Avastin® Woes

    By Kevin E. Noonan --

For the past several months, Genentech has been assailed by ophthalmologists and patients over its decision to ban compounding pharmacies from reformulating its anticancer drug Avastin® (bevacizumab, a monoclonal antibody) to be used for treating neovascular or "wet" age-related macular degeneration (AMD), a condition that if untreated leads inexorably to blindness (see "Genentech Acts to Halt Off-label Use of Avastin® for Age-related Macular Degeneration").  This use of Avastin® is an off-label use; Genentech makes a related drug, Lucentis® (ranibizumab injection), that 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 it is injected into the eye at such small doses (0.1cc) that each vial can deliver 30 doses ($20/dose).

Although initially defending their decision (see "Genentech CEO Defends Differential Cost for Avastin®/Lucentis® Treatment of Macular Degeneration"), more recently the company has responded in a more conciliatory way to the outrage, protests, and threats of political and legal action from its customers and their physicians (see "Age-related Macular Degeneration Patients Get a (Limited) Reprieve").  For example, the company recently postponed the deadline for its compounding pharmacy ban from November 30th to the end of the year.  It has also taken steps to explain its position to organized ophthalmology groups like the American Society of Retinal Specialists (ASRS) and American Association of Ophthalmologists (AAO), particularly with regard to the relationship between its ban and 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.

While these latest actions have been applauded by these organizations, the decision to ban compounding formulary from diluting Avastin®, and the original handling of the decision and how it was presented to the AMD community, prompted threats of political action.  It seems that despite its efforts to recoup lost goodwill, Genentech now faces just this kind of political action.  On October 18th, Senator Herb Kohl (D-WI) (at left), Chairman of the Senate's Special Committee of Aging, sent a letter to Kerry Weems, Acting Administrator of the Center of Medicare and Medicaid Resources regarding the proposed ban.  Citing an October 12th Wall Street Journal article on the topic, Senator Kohl termed Genentech's decision "troubling," particularly since he understood the action was taken to boost sales of Genentech's Lucentis®.  The Senator cited a particular portion of the Journal article that predicted an increase of from $1 billion to $3 billion per year in Medicare costs due to the ban, and stated that any action that would impose such increased costs on American taxpayers concerned him.  Senator Kohl also cited testimony from another physician's group, Physicians for Clinical Responsibility, regarding Genentech's lack of cooperation with a National Eye Institute study comparing the efficacy of AMD treatment between Lucentis® and Avastin®.

The Senator was clear about what he wanted:  he asked Administrator Weems to provide the answers to two questions:

1.) How much has Medicare spent on Lucentis and Avastin during the period 2005-present?

2.) What measures, if any, have CMS officials taken to explore the reduction of expenditures on expensive drugs such as Lucentis by using alternative treatments such as Avastin?

Senator Kohl ended his letter by saying that saving taxpayer dollars was of the "utmost importance," implying further action if he and his committee did not receive satisfactory answers.

And if that weren't enough bad news, on Monday the Food and Drug Administration's Oncologic Drugs Advisory Committee released a report that showed that even though Avastin® slowed the spread of metastatic breast cancer in the breast cancer sufferers in the study, it did not increase overall survival times.  At the same time, including Avastin® with more conventional breast cancer chemotherapeutic treatments, such as paclitaxel, increased (by 20%) the incidence of serious side effects, including heart attack, stroke, bleeding, and other complications, including six deaths in 363 study subjects.  An advisory committee voted 5-4 yesterday against approval of Avastin® for combination chemotherapy in breast cancer.  Although the final decision will be made by FDA, the agency typically follows the advice of its advisory committees, which are made up of physicians and other experts.  It is thus possible that Genentech's problems over the Avastin®/Lucentis® situation are far from over.

For additional information on this topic, please see:

• "Age-related Macular Degeneration Patients Get a (Limited) Reprieve," November 7, 2007
• "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

Comments

Why do all accounts of this issue fail to state that the lucentis is a monoclonal antibody fragment derived from the same parent? Anyone reading this story should be informed that lucentis is in bascially a portion of avastin.

[Kevin E. Noonan]

Dear :

You're right, of course, but I'm not sure that is particularly relevant. Avastin clearly works, and at a much lower price, but was not put through the same clinical trials as Lucentis (that's the FDA piece), and NEI is trying to do a study to show the two drugs have equivalent safety and efficacy. Even if they were totally different molecules, the point is a cheaper, anecdotally as-effective alternative exists. And the story is the company's attempts (justified or not) to have AMD patients use the more expensive one.

Thanks for the comment.