Wednesday, October 31, 2007

Retinal Specialists Get the Integrity Award--Genentech and Avastin

I am rather shocked to look back in the blog archives and see that I have not yet addressed the Avastin-Lucentis controversy. So I need to provide some background before handing out today's integrity award.

Quick overview--Genentech, the biotech firm, is maker of a very successful drug (brand name: Avastin) that is quite useful in colon cancer. The drug works by counteracting the tendency of tumors to create a lot of new, small blood vessels to keep the growing tumor supplied with blood. Some smart person figured out that the eye disease called wet macular degeneration is caused by a similar proliferation of new blood vessels and so the same sort of drug might help that condition too. (Wet macular degeneration occurs mostly in older folks but is not the most common sort of macular degeneration, a common cause of progressive vision loss. Still it affects a large number of people.)

So some retinal specialists tried Avastin by injection into the appropriate area of the eye and found that it really worked just great--highly effective and apparently very safe. The special bonus was the price. Avastin is extremely expensive for colon cancer, costing many thousands of dollars for a course of treatment. But the dose you need to treat an eye is a tiny fraction of the dose you need for colon ancer. So a single very expensive vial of Avastin can produce hundreds of relatively cheap doses for eye use.

Genentech had figured out the marketing angle on this pretty early on. They first did the usual "evergreening" trick, figuring out what portion of the Avastin molecule was the business end and creating a smaller molecule that contained that active portion. (Brand name for the new fragment of the old drug: Lucentis.) They then, based on some suspect animal data, declared that they just knew, without doing any further studies, that Avastin was too large a molecule to penetrate into the eye where it was needed. That was the excuse they used for not subjecting Avastin to any formal scientific trials to see if it worked in the eye. Then they did studies of Lucentis and showed that (surprise) it did work pretty well in the eye, and so they marketed Lucentis with a specific label saying this form, and only this form, was for eye use. Of course, since Lucentis was intended for eye use only, they prepared it in very tiny vials, each containing enough for one treatment, and priced each vial at a hugely expensive figure. Somebody calculated that at the price charged for Lucentis by Genentech, if all people with wet macular degeneration got treated with that drug, the entire present-day Medicare budget for eye treatment would go into the pockets of Genetech.

Now, stop for a minute and think what the average retinal specialist out in community practice is facing in the choice between Avastin and Lucentis. All the Genentech reps are heavily pushing Lucentis and giving a whole slew of phony reasons why Avastin is no good for eye use. We presume that there was all the usual bribery with fancy "educational" conferences at plush resorts for those who prescribed Lucentis. Coupled with all that marketing pressure is the threat that if any of them use Avastin in the eye, and there are any bad consequences, they'll have the pants sued off them for using an off-label drug that was not FDA approved for this purpose.

So if the retina guys acted like most docs act most of the time, when faced with the juggernaut of Pharma marketing, they would all be using Lucentis, and the patients and Medicare would be going bankrupt.

But that is not what happened. Despite all this pressure, the obvious rightness of using the good, cheaper drug continued to win out, and a significant number of specialists were using Avastin for wet macular degeneration and passing the savings along to the patient or the insurer.

Genentech was furious that the docs were refusing to be bribed, as usual. They cranked up their campaign, threatening to cut off supplies of Avastin to anyone who was making it available for eye use. They did this of course not for slimy financial reasons, but for good scientific reasons because they wanted to promote the very best quality of care.

On October 29, the American Academy of Ophthalmology put out a news release:

The AAO and the American Society of Retina Specialists sent a high level delegation to meet with the Genentech bigwigs. Genentech agreed to hold off its threatened sales embargo, not to impede physicians or pharmacies seeking to use Avastin, and to seek advance comment from the two societies before putting out any new statements comparing Avastin to Lucentis. (Genentech, for its part, indicated that it was working in tandem with FDA guidance and that depending on what the FDA did or did not approve, it might later rescind this agreement.)

It is not clear what will happen in the future. A clinical trial to compare Avastin and Lucentis head-to-head for wet macular degeneration is now underway, with neutral funding I believe. In any event it seems that retinal specialists have as a group been singularly impressive and successful in standing up for the patient.

1 comment:

Irv Arons said...

For more on the head-to-head study, being funded by the National Eye Institute, please see my web Journal.

Here is the link:

Also, more on the Avastin vs Lucentis controversy can also be found on my Journal:

Irv Arons