Genentech CEO Defends Differential Cost for Avastin®/Lucentis® Treatment of Macular Degeneration

    By Kevin E. Noonan --

The comparative effectiveness of two Genentech drugs, Lucentis® and Avastin®, for the treatment of age-related macular degeneration (AMD) is currently the subject of a study by the National Eye Institutes (NEI) of the National Institutes of Health.  The reason:  the cost of Avastin® treatment (an off-label use, since Avastin® is approved only for treating colon and certain lung cancers), is much less than the cost of treating AMD with Lucentis® ($20-60/dose versus $2000/dose).  Perhaps not surprisingly, Genentech has refused to supply the NEI with either drug for the trial.  In an article in Tuesday's Wall Street Journal, Dr. Arthur Levinson attempted to justify the decision.

In responding to questioning by reporter Marilyn Chase, Dr. Levinson (at left) recounted the history of the development of both drugs.  According to Dr. Levinson, Genentech's inventor, Dr. Napoleone Ferrara, purified vascular endothelial growth factor (VEGF), a protein that induces blood vessels to form, and then showed that 90% of cancers overexpressed the protein.  This discovery was consistent with work, most famously by Dr. Judah Folkman, that cancer cells produce angiogenic factors that induce blood vessel proliferation in tumors as part of the natural progression of the disease.  Avastin®, a monoclonal antibody that interferes with VEGF action, was then developed by Genentech for use against colorectal and lung cancer.  The same Genentech inventor also showed (about 12 years ago) that patients with macular degeneration also have high levels of VEGF, in this case near the retina, which led to the development of Lucentis®, another antibody-based drug.

Dr. Levinson pointed out that, despite this coincidence of disease etiology (i.e., inhibiting VEGF as a way to prevent unwanted vascular proliferation), bringing Lucentis® to market required two years of experimental work to improve binding affinity to VEGF, reduce the molecule's size and make it noninflammatory.  In addition, the drug had to undergo a full regulatory review (Phases I, II and III of the Food and Drug Administrations IND/NDA approval process), and was not approved for use in treating AMD until June 30, 2006.  Dr. Levinson also noted that the Phase III clinical trials for Lucentis® were, in his words, "the most expensive clinical-development program Genentech ever undertook," costing $40,000 - 45,000 per patient.

In Dr. Levinson's view, the cost of Lucentis® is the result of all these factors, and as such is fully justified.  He also questioned the wisdom of spending the upwards of $50 million it will cost to do the NEI trial, in view of a finite U.S. R&D budget and the overwhelming number of other diseases having no or ineffective treatments.  Finally, he disputed allegations that some patients did not have access to the more expensive Lucentis®, citing coverage by major health insurers and the company's own drug purchase assistance programs.

Dr. Levinson's points are well-taken, but in the current climate it will be hard for his comments to change many minds.  Genentech is faced with defending a situation where its drugs, both Lucentis® and Avastin®, are two of only three drugs effective for treating AMD.  (The other is Macugen, sold by (OSI) EyeTech, Inc., which has a far smaller share of the market).  As Dr. Levinson acknowledged, "[t]his is a disease that over the course of days you can go from 20/20 vision to losing your eyesight.  It's very, very quick, and once you lose your vision, it's gone and you will probably never get it back."  In addition, neither drug cures AMD but merely stabilizes it, preventing the condition from worsening in many patients.  As a consequence, the drug must be administered like insulin or other maintenance drugs.  At a cost of $2,000/dose and a once-a-month dosing schedule, the cost to treat the half-million "wet" AMD patients in the U.S. with Lucentis® is greater than $10 billion per year.  Avastin® treatment is cheaper because a vial of it costs less ($600/vial) and each vial yields more doses, according to Dr. Edward Chaum, Plough Foundation Professor of Ophthalmology, University of Tennessee (as previously reported in Patent Docs).

Genentech's decision will do little to either resolve the controversy (which includes assertions by the company that Avastin® treatment entails significantly higher risks of side effects including stroke), nor diminish the anger in the retinal ophthalmology community over the company's stance.  Nor will Genentech's decision not to support the NEI study inhibit these ophthalmologists from off-label use of Avastin® for treating AMD.  All the decision will do is limit the comparitors between Avastin® and Lucentis® treatment to anecdotal evidence from off-label Avastin® use, and give additional ammunition to those who unfairly ignore the realities of drug development by focusing on the purported avarice of the innovator drug companies responsible for developing new drugs.  It is not in the public interest to frame the debate in this way, but neither is that interest served by Genentech's refusal to support the NEI's study and conform its behavior to that study's conclusions.

For additional information on this topic, please see:

• "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

[IrvArons]

For more on this controversay, please take a look at my web Journal at:

http://irvaronsjournal.blogspot.com

Irv Arons

[Michael Stur]

Just a small calculation:
if the trial DID cost 45.000 $ per patient, its cost has been more than covered one day after the first day Lucentis vial was for sale. EACH patient who receives lucentis will need an average of 10 (ten) injections within 24 months, and these injections cost 20.000 $ !! So actually the statement by Genetech was simply a confession that the price of Lucentis is way over the limit, at least by a factor of five, maybe ten ...

Genentech could avoid the comparison trials by lowering the price of Lucentis to 200 to 400 $ per shot. They would easily sell ten times as much as today and would have the market for the next ten years.

As long as Lucentis is so expensive, we will have to use Avastin. And Avastin from being inferior...

Just my 2 c

Michael Stur, MD
Medical Retina Specialist

[Barry Wheeler]

Mr. Stur, I had to agree with you in your statements. GenenTech is truly pricing themselves out of the market when the two drugs are practically identical. One must question their reasoning for doing this.

If we look at the burden that this will pass onto the taxpayers in provinces such as Ontario, Canada where Lucentis has now been approved as the treatment for wet macular degeneration under their health care plan, one must wonder how long such public systems can sustain this.

Can the difference in the two drugs be shown after they have been administered?

Barry Wheeler
http://www.amdsupport.ca/

[Lasik Austin]

Yeah that is somewhat of a challenge because with the pricing being so much different people are naturally going to use the more cost effective option. It is good to know that Lucentis is a far better drug though.

[Bruce W. Maynard]

The cost of the Lucentis drug is cost prohibitive for WMD. This drug could cost me $7,200 dollars a year with my co-pay. Without a co-pay it would cost $36,000 for 12 shots.
It cost according to the developers of Lucentis $40,000 to $45,000 dollars for clinical trials.
If 50,000 patients received an injection at $2,000 dollars (cost the drug company claims)that is $100,000,000 in one week. Times 52 weeks that equals 5,200,000,000 in a year. Using very conservative numbers to compute this total tells me it is probably 5 fold of the above number. This is obsene.