Wednesday, May 21, 2008

Avastin/Lucentis Update 23: An Interesting Overview of the Controversy

Someone recently linked to this Journal from a website I hadn’t looked at in over a year, HealthDot@ScribeMedia, and its writeup entitled: Genetech’s Two Headed Monster: Lucentis and Avastin, (which I reproduced, with permission, on March 3, 2007, as Avastin/Lucentis update 13). In re-reading some of the comments at the end of the article, I found Dr. Gregory Rosenthal’s comments to be quite interesting and seemed to sum up what many, including me, felt about the situation at the time, and partly why I’ve put so many updates on this subject on this blog.

Dr. Rosenthal is a staff member of Vision Associates of Toledo, Ohio and one of the co-authors of the White Paper, Avastin versus Lucentis: Why It Matters. (This can also be found on my website as Avastin/Lucentis Update 11.)

Here is Dr. Rosenthal’s commentary as published at the end of Genentech’s Two Headed Monster: Lucentis and Avastin (which included an audio interview with Dr. William Rich of the AAO on the Avastin vs. Lucentis controversy).

I was very interested to hear Dr. Rich’s interview. Bill is a real voice of integrity in our field. As I listened, I couldn’t help thinking about what seems like a break in logic.

Here are the premises:

1. Genentech’s folks are brilliant and they have made a fantastic drug in Avastin and recreated it in Lucentis. They say that they tested an Avastin precursor before developing Lucentis and it didn’t penetrate monkey retina so they just figured Avastin would never work in the eye. (How convenient.)

2. They are very (appropriately) proud of their ability to know EVERYTHING about their drugs and engineer them for optimum patient benefit.

3. Phil Rosenfeld is also a brilliant guy. Unlike these proud and brilliant Genentech guys, he figured out in just a patient or two that Avastin not only works in the eye; it is quite miraculous. This and the safety of Avastin have been corroborated over and over by other brilliant people in peer reviewed reports since then.

Here are the obvious facts:

1. Genentech knew that, in Avastin, they had a true wonder drug for cancer.

2. They knew that it would be priced appropriately for 500 to 1500 mg doses every two weeks, guaranteeing them billions in revenue.

3. They knew or could figure out (hey, it’s simple arithmetic) that IF Avastin would work in the eye, we’d only need 1 mg or so, meaning that, at the pricing they would be stuck with from the cancer indication, they wouldn’t make any money.

4. They knew Novartis was making billions with the pricing precedent they set with Visudyne, and it doesn’t even work that well.

So, here’s the questions:

1. Is it possible that the oncology pricing could have been seen as a problem for ophthalmology marketing?

2. As a for-profit company, what would have been the motivation to even see if Avastin worked for AMD? Might there have been greater motivation to NOT look at Avastin and just extrapolate a conclusion from perfunctory testing of a precursor in order to make some plausible claim that Avastin was worthless for the eye?

3. Would that have cleared the way to take a drug with an active site that they KNEW was good, alter it, give it a new name, and bring it out as “something else”, with, of course, a new price, once again guaranteeing billions more in profit from essentially the same molecular active site?

These are NOT accusations, just musings on the seeming illogic of the brilliant folks at Genentech missing something so obvious, and the odd coincidence that missing this could result in up to $10 billion per year in additional revenue. Boy, I’d give a nickel to see the e-mails at Genentech about ten years ago, just to see what they knew and when.

Wait, $10 Billion with a “B”? Sure. They are projecting $1 billion for ‘07 when 79% of docs use Avastin half as often as Lucentis – $1 billion X 5 X 2 = $10 BILLION per year, or about twice the CMS budget for ALL of eye care. Even at only $1 billion per year, it will break the bank for many seniors and I would guess more than a few payers.

Thanks for putting up a great website.

Posted by Greg Rosenthal, MD | March 6, 2007, 3:07 pm