A Staring Contest Between Genentech & The FDA
11 CommentsBy Ed Silverman // June 17th, 2008 // 6:12 pm
Last year, Genentech caused a ruckus by restricting distribution of its Avastin med to compounding pharmacies, which were repackaging and selling the drug to opthalmologists for treating wet macular degeneration. Unlike Avastin, Genentech’s similar, but newer Lucentis was approved to treat the malady, but at $2,000 a dose will cost about 40 times as much.
The drugmaker subsequently struck a deal with opthalmologists to loosen the restrictions. But in explaining its original rationale, Genentech cited an FDA inspection that found 350,000 vials worth about $200 million were “unsuitable for use in the eye,” but the drugmaker insisted the lots “would have been entirely suitable for its approved use as an intravenous cancer medication.”
As a result, Herb Kohl, the Wisconsin Democrat who chairs the Special Senate Committee on the Aging, began investigating the cost to Medicare if Avastin usage was restricted. In an FDA letter sent to his staff, the agency writes inspectors “identified deficient practices and the lack of of effective processes to know what was in those four lots. Consequently, the agency recommended that those lots should be considered unfit for use for any indication.”
The letter was referred to in a memo written by Kohl’s staff about the Avastin controversy. The memo, which we have reviewed, also notes that a separate issue concerning the FDA inspection involved “levels of glass particulates in the Avastin lots in question (which) were a central issue in the ultimate decision to destroy those particular lots or vats of the product.”
Another internal agency e-mail from a high-level FDA eye expert stated explicitly that “Genentech has found a way to blame FDA for their decision to limit the distribution of Avastin. The manufacturing problem at their facility that resulted in glass in their product would be an issue for either the on label oncology indications or the off label ophthalmology indications,” the senior FDA official wrote to his colleagues, according to the memo.
“We have to respectfully disagree with the FDA’s opinion and that they were safe for intravenous use for cancer based on our guidelines for oncology. There are two points of view on this inspection,” a Genentech spokeswoman tells us.
Genentech cites another reason for changing distribution - a warning letter the FDA sent to a New England compounding pharmacy that was repackaging Avastin. The drugmaker cites that episode to justify its position that Lucentis is the appropriate treatment for wet macular degeneration, an argument apparently taken to the FDA.
According to the Senate memo, internal FDA e-mails revealed Genentech “approached (the) FDA a year ago to change the Avastin labeling to explicitly state Avastin is not intended for ophthalmologic use, but that (the) FDA had felt at that time that there was no safety-related basis adequately justifying that labeling change.”
An FDA spokesman hadn’t returned our call by the time we posted this.
Hat tip to the WSJ Health blog
Robert Bird
How is product containing glass more safe for anticancer uses than for ocular use? People are more willing to tolerate glass when they have cancer than when they’re going blind?
This sounds like drunk logic at its finest.
Dan
The vials increase the longevity of the drug by allowing a longer expiration date.
Biopharmaceuticals are expensive. Genentech’s drug Avastin for cancer costs 100,000 a year, as well as for off label macular degeneration, with minimal benefit. Avastin for the eye disease is from 100 to 200 dollars a dose. Thier newer Lucentis, that is very similiar to Avastin, is being charged about ten times the price of Avastin.
Biotechs in general need to justify thier cost. With cancer biotech therapies, they generally extend life by only a few months for cancer pts and are used with chemotherapy.
I’m not sure it is worth that amount of money for such minimal benefit.
CMC guy
Robert not sure yet I believe there are different “particulates” specifications for opthalmologics verses injection use and thus would assume there may be values acceptable for the later but not former application (assumes opthalmolics is more stringent which I think is correct). There are allowances for some particles however finding glass is a more serious matter and speaks to bigger problems in manufacturing.
The statements above are a bit confusing as I thought the rationale for not having Avastin for off-label use was because loss of several lots created a “shortage” so restricted distribution availability.
Paul G
I think you are all mixing up the issues here.
Issue #1: Avastin has never been studied for ophth use, so there is no data on efficacy or safety or dosage or AEs or anything. So not sure how anyone can be expecting the company to promote it for that use. If they di, I am sure they would have the feds at the door in no time.
Issue #2: As I understand it, compounding pharmacies have been taking vials of Avastin and taking little bits and putting into other vials to sell to ophthalmologists who inject the product off-label. The report posted by Ed seems to indicate that people are worried about having a product not tested in the eyes used there.
Can’t have it both ways: criticize companies for promoting off-label and at the same time criticizing companies for not promoting off label.
Bingo
Paul,
The criticism is not about off-label promotion. It’s about an attempt to limit legitimate off-label use of one product in order to stimulate demand for a vastly more expensive, yet very similar product.
harpy
Unfortunately, there is no such thing as “legitimate off-label use” for the company. In fact, selling Avastin to compounding pharmacies can be a reason to investigate them for off-label promotion and, consequently, false claims. They were able to get away with it for a while, obviously, but to continue to sell to compounding pharmacies when they knew it would be for off-label use is dangerous water for the company.
And I don’t know what Senator Kohl is thinking - is he berating the company for not breaking the law? Not that I think Genentech is wholly innocent - they’ve obviously got the $$$ in their eyes.
Bingo
Harpy,
You are mistaken in this case.
They have absolutely no incentive to promote the off-label use of Avastin in direct competition with their own Lucentis product.
The two compounds are closely related, so a fraction of a vial of Avastin can be used instead of a much costlier dose of Lucentis.
There is a big difference between off-label use and *promotion* of off-label use.
harpy
Actually, Bingo, I think you’ve missed my point. I know they have no incentive, but when a company sells a product in a way that is completely out of line with its indication, it is seen as off-label promotion. So the question is whether Genentech has a legitimate reason, not related to treating wet macular degeneration, to sell its product to compounding pharmacies. If yes, well, they’re being shady, if no, then they’re covering their @sses.
While the company is no longer selling to compounding pharmacies there is nothing to stop doctors from buying the drug and making an arrangement with a compounding pharmacy. This would be off-label use.
And, again - I don’t think Genentech is right to charge Lucentis 40x what Avastin costs for the same treatment.
David Hamilton
Genentech previously distributed all of its infused oncology drugs through compounding pharmacies, so I think the FDA would be hard-pressed to complain that this particular instance represents an example of off-label promotion. (In fact, the company’s official explanation for the change with Avastin is that it wanted to streamline its oncology-drug distribution, primarily for product-security reasons; see David Williams’ interview with Genentech spokeswoman Dawn Kalmar last November.)
Williams also identified the 2006 FDA warning letter to the compounding pharmacy in question (the New England Compounding Pharmacy), although the link has succumbed to linkrot, as the FDA now apparently only keeps two years of the letters on the Web. (Which is stupid in its own right.) According to his account, the letter wasn’t primarily about Avastin, which was mentioned fourth in a list of concerns.
Genentech’s explanations for its treatment of Avastin here still don’t make sense, particularly in light of the FDA correspondence leaked by Kohl’s office (which still isn’t available on the Web so far as I can tell). Coupled with its refusal to participate in the head-to-head NEI trial, which of course pushes up the cost to the federal government, it looks very much like the company is fighting a rearguard action to put up as many obstacles to ocular use of Avastin as possible.
I’ve written more here.
Irv Arons
Anyone who is interested in reading more of the “back story” of the controversy over the use of Avastin and Lucentis can do so on my web Journal (http://irvaronsjournal.blogspot.com).
I have 25 articles on this controversy, as well as several updates on the CATT Study, sponsored by the NIH/NEI that is in the process of comparing the two drugs for treating the wet stage of age-related macular degeneration.
For easy access to the articles, just print “menu” into the search box in the upper left hand corner of the home page and all of the menus containing the articles will show up.
Irv Arons
harpy
Thanks for the explanation, David. It does cast the company in a bad light.