The following commentary appeared on June 6, 2007 in the Patent Docs Biotech & Pharma Patent Law & News Blog. It was written by Attorney Kevin E. Noonan. It is reproduced with permission of the author.Genentech CEO Defends Differential Cost for AVASTIN/LUCENTIS Treatment of Macular DegenerationThe 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 today's (June 5, 2007)
Wall Street Journal, Dr. Arthur Levinson (Genentech’s CEO) attempted to justify the decision.
In responding to questioning by reporter Marilyn Chase, Dr. Levinson 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 induced blood vessels to form, and then showed that 90% of cancers overexpressed the protein. This discovery was consistent with work, most famously by 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 EyeTech (now owned by OSI Pharmaceuticals), 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 stablizes 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 its stance. Nor will this 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.
