Last week the New England Journal of Medicine published the study eye care professionals have long been waiting for, comparing treatments for macular degeneration (AMD). The CATT study (“Comparison of Age-Related Macular Degeneration Treatments Trials”) was funded by the American National Eye Institute (NEI) to compare Lucentis and Avastin head-to-head in the treatment of AMD. 

AMD is the leading cause of blindness in Australia and affects 1 in 7 people over 50. The most aggressive form, “wet” AMD, was for years effectively untreatable, until Lucentis was developed. Lucentis is a monoclonal antibody fragment (Fab) that binds to a protein called VEGF. We need VEGF to produce new blood vessels in the body, but when it is over-produced it can cause diseases such as AMD, proliferative diabetic retinopathy and retinopathy of prematurity. While ophthalmologists were waiting for the FDA (the US regulatory body controlling medicines) to approve Lucentis, they began using Avastin, a Fab that comes from the same parent molecule as Lucentis, and which is usually used in cancer treatment. They found it worked very well for AMD.

Most ophthalmologists have long believed that Avastin is as good as Lucentis for treating AMD, and it is considerably cheaper (US$50 compared to US$2000 per dose), but since Lucentis gained approval and PBS listing in Australia it has been far more widely prescribed. Avastin remains unapproved for AMD and in Australia its ophthalmic use is limited to management of diabetic retinopathy and retinal vein occlusion, and in public hospitals where PBS benefits don’t apply. The makers of Lucentis insist that Lucentis is better, although a year’s treatment with Lucentis costs more than US$20,000 and a year’s treatment with Avastin costs around US$400.

Wouldn’t you think that the makers of Avastin would try and show that it is equally good and seek to have it approved for use in AMD? Well, here’s the problem: Lucentis and Avastin were both developed by Genentech (based in San Francisco but now owned by Swiss giant Roche), although Lucentis is sold in Australia by Novartis. Since Genentech spent US$1.2 billion developing Lucentis, it is simply not in their interests to encourage the use of a drug that costs 40 times less. When Avastin is used in cancer treatment much larger doses are given, and Genentech already earns around US$2.5 billion annually from its sale.

So it has been left to the publicly-funded NEI to produce the first good randomised controlled trial (RCT) of Lucentis v Avastin, the CATT. It’s a very well designed study that recruited 1208 patients, and compared the two drugs across two regimens. They came out equal in their ability to treat AMD and restore or maintain vision. There were slightly more hospitalizations in the Avastin patients (24% compared to 19%), and this needs more study.

Both drugs work very well in the management of “wet” AMD, and have revolutionized the treatment of patients with this debilitating disease. We now know that they are equally good. But the importance of this study also extends to the public health sphere, where politicians and health bureaucrats need to try to do more and more with less and less. There were almost 130,000 scripts for Lucentis dispensed in Australia in 2010, costing the Australian taxpayer more than $220 million through the PBS subsidy. If the same patients were treated with Avastin, an additional $214 million dollars would have been available for other health problems. Perhaps for disability support services, mental health, or indigenous eye care?

It also brings into sharp focus the complex nature of our relationship with the pharmaceutical industry, whether as doctors, optometrists or patients. We need the industry to invest in Research & Development, and the industry needs to be able to realize a profit to justify that initial investment, or new drug development will decline. But we can’t always rely on the industry to deliver value, and conflicts of interest can occur. We need to be aware that pharmaceutical companies are still primarily answerable to their shareholders, not to their customers, our patients. 

(Article citation: The CATT Research Group. Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration. N Engl J Med. 2011 Apr 28. [Epub ahead of print])