Age-related macular degeneration is a leading cause of vision loss and blindness. The advanced form of the disease affects 1.6 million people in the United States. That’s why results from the first year of a two-year clinical trial that tested medications for the wet form of age related macular degeneration (AMD) look promising for patients:
1. In comparison with previous treatments, Avastin and Lucentis are the first treatments to ever improve vision in patients with age-related macular degeneration;
2. Drugs used in the past (Macugen and Visodyne) only slowed the progression of age-related macular degeneration.
3. Testing various regimens, including monthly injections versus variable (stopping the injection if no fluid builds up in retina), investigators learned that they could give injections into the eye less frequently than once a month because patients getting the injections did not build up fluid that quickly. On average, patients needed injections into their eye 7 times during the year, instead of monthly (or 12 times).
4. The two drugs had about the same effects on visual acuity, when administered on the same schedule.
5. The drug’s cheaper formulation (Avastin), cost $50 per injection, compared with Lucentis, at $2,000 per dose.
6. Safety considerations are still being evaluated. Serious adverse events (primarily hospitalizations) occurred in 24 percent of patients for patients on Avastin, compared with 19 percent for patients on Lucentis. According to the study, these safety concerns were not identified in previous studies of Avastin, when used to treat colon cancer. Patients are now being followed for a second year and safety will continue to be monitored.
A Patient’s View of the Clinical Trial
I spoke with Mara Coon, participant in the drug trial at the University of Wisconsin Madison site, for the Comparison of Age-related Macular Degeneration Treatments Trial (CATT). She is 74, was diagnosed with the wet form of age-related macular degeneration two years ago, and she told me that she let her first eye go before she entered the trial. She likes to do a lot of reading and knitting. Because the trial has a year to go, she does not know which drug she is taking. Her vision was 20/60 when she entered the trial, but after a year on the injections, it varies between 20/20 and 20/25. She was quick to tell me: “I am not sure whether everyone responds as well as I do,” a point of view that I think should be underscored. She likes participating in the trial, saying that “if it helps someone down the road, I am happy.” Suresh Chandra, MD, professor of ophthalmology at the University of Wisconsin, pointed out that is the “first time that we have seen a visual gain.”
Readers may recall that only a few years ago, Avastin, given at 500 times the dose for macular degeneration, was considered a miracle drug for advanced breast cancer. The drug costs for a year of treatment with Avastin average about $90,000 to $100,000. In the setting of breast cancer, Avastin has had a rocky road: to date, benefit in progression-free survival shown in the original study has not been replicated. Moreover, using disease-free survival, surviving without evidence of disease, not overall survival, or how long the patient actually lived, is a controversial measure of a drug’s effectiveness for terminal cancer.
Avastin was considered a breakthrough drug for treating cancer. It has been studied in a huge number of trials, both in cancer and for other diseases that depend on a rich blood supply. Avastin’s mechanism of action is to prevent new blood vessel growth that allows cancerous tumors to develop and and spread. In 2004, the FDA approved Avastin for the systemic treatment of metastatic colon cancer. In the course of using Avastin for colon cancer, investigators noticed that the drug also helped block blood vessel growth in age-related macular degeneration. Avastin was not approved by the FDA for the indication of AMD, but in 2005, Lucentis was established as highly effective for the treatment of wet AMD in clinical studies. Avastin was approved by the FDA in 2006 for AMD.
Cost and pricing are thorny issues. For macular degeneration, Avastin costs $50 per dose, compared with $2,000 per dose for Lucentis, but the outcomes are essentially the same. Many doctors do not want to discuss costs with patients. Perhaps patients also feel so removed from prices unless they have high out-of-pocket costs that they don’t think much about them either.
Several ophthalmologists declined to be interviewed for this story. The American Academy of Ophthalmology issued a press release the same day as the study was released, titled “New Study Offers Hope and Treatment Choices for Macular Degeneration.” The press release also states: “For unknown reasons, some wet AMD patients do not respond to one drug but get positive results with the other. Eye MDs need the flexibility to prescribe either medication to provide the best care for their patients.” This needs to be explained fully so the best decisions are made.
Patients should be aware that some ophthalmologists are consultants to drug companies or medical device manufacturers. Many doctors who work with industry do so because they want to participate in developing advances in their field. Yet these issues are not black-and-white. The public pays for these advances; drug companies invest in them, and reap the profits or take losses.
Pricing Macular Degeneration Drugs
Thus far, many articles and blogs have discussed the two drugs as if they are very different. However, they are made from the same monoclonal antibody; they are not different drugs at all. Ranibuzumab, the generic name for Lucentis, is made by customizing the molecule in bevacizumab (Avastin). According to the package inserts, they are manufactured in different cell cultures. The actual manufacture of Lucentis should not be that much more costly, according to several physicians, who asked that I not name them. What undoubtedly goes into price are research and development costs to bring the drug to market, including amortization costs (reduction in operational costs associated with evaluating the drug), patent life, and drug competition. Both eye medications are made by Genentech.
Pricing for this group of macular degeneration drugs and drugs with similar impacts, merits, and costs are likely to be debatable, both in the United States, which is struggling with health expenditures, as well as resource –poor countries. The burden of having advanced macular degeneration is blindness. Around the world, numbers are enormous.
How will countries pay for drugs like this and many more in the pipeline? “Insurance companies are going to say: ‘Why do you want to use Lucentis?’” said Chandra. Even though he acknowledged that Genentech has invested in research, he added: “We are talking about billions versus millions.” He said that the trial results offer a “big sigh of relief for developing countries.”
Sean Tunis, the founder and director of an independent nonprofit organization, the Center for Medical Technology Policy, and a proponent of what is called “value-based” or “outcomes” pricing, does not think that the horse is out of the barn. In a nutshell, value-based pricing would consider payment for clinical outcomes. Tunis does not think that the “value-based price” for Avastin is $50, and he called reporters who stopped there in their cost discussion “hypocritical.”
“This is the first treatment to ever improve vision for macular degeneration,” said Tunis.” That is worth a lot more than $50 per dose.” The cost was figured, based on per milligram, not per outcome, he explained, proportional to say, how much less is needed to inject into the eye than is required for cancer indications.
There is a movement afoot in healthcare reform to pay for care, based on how well interventions do in achieving the best clinical outcomes, and paying attention to clinical outcomes that are most important to patients. Tunis also pointed out that there is a “small safety signal,” referring to the 24 percent versus 19 percent hospitalization rate in the trial.
This is a pretty complicated story. It is far from over. We have only seen safety and outcomes with these drugs for one year. It’s a start. What do you make of it?