Just about a year ago, I reported the one-year results for the Comparison of AMD Treatments Trial (CATT), which compared Lucentis, the high-cost injectable medication made by Genentech with Avastin, also made by Genentech. A lot has happened in the past year in macular degeneration, including the release of two-year CATT results and the approval of a new drug, Eyelea, by Regeneron.
Your Ophthalmologist’s Biases
Doctors talk about patient-centered care, but I am starting to think that patients are out in the cold in terms of picking the best doctors for themselves. We know zero about physician biases, use of data, and involved with pharma and medical device manufacturers.
If you’ve got wet macular degeneration and are a candidate for drug therapy, you may find yourself lost when you search for an ophthalmologist to treat you.:
- How do you pick a top-quality ophthalmologist?
- Are the drugs affordable?
- What are your preferences?
- Does your ophthalmologist have preferences for specific drugs and are those preferences aligned with your’s?
- Will your ophthalmologist recommend therapy, based on the best science and safety data?
- Is affordability important to you? Your out-of-pocket costs can be substantially higher with Lucentis, for example.
Much harder to discern is what your doctor’s biases are. For all the talk about ratcheting up patient literacy, patients know next to nothing about ophthalmologists’ biases. There are no uniform standards. I’d like to see more transparency. For example, is your ophthalmologist going to pick a brand name on principle? Pharmaceutical sales reps will press safety buttons, making your physician go with brand. Is your ophthalmologist a paid consultant for the eye industry and could this bias his or her perspective? Are ophthalmology sales reps sitting in the waiting room? Are promotional literature, pens, and tissue boxes cluttering up the waiting room? It would be nice to know their involvement with industry: speakers’ bureaus, patents, involvement with drug and device companies.
It’s not just your ophthalmologist.
Your Doctor and the Pharmaceutical Industry
According to a report in the Nov. 3, 2010 New York Times, Genentech used a secret rebate program for eye doctors dispensing a high-volume of Lucentis, and rebates rose as quarterly usage increased.
I am not naïve enough to think that I can find a pure eye doctor not involved with industry in any way, shape, or form. I have been to too many ophthalmology meetings and read the disclosures to expect it. I want an eye doctor attentive to my out-of-pocket costs and not recommending a drug because s/he is on a speakers’ bureau or because a drug rep promoted it as the only safe option, when it is disputable.
Is it too much to ask for patients to have the same information on industry involvement available to us that medical journals require?
5 Fast Facts on Wet Macular Degeneration Drugs
1. Currently, there are 3 drugs available demonstrated to improve vision: Avastin, Lucentis, and Eyelea.
2. “Lucentis accounts for 10% of Medicare Part B,” state the CATT authors in the two-year trial results, a higher proportion than I ever expected.
3. Medicare reimburses ophthalmologists 6% of the average wholesale price of the injected drug, or $120 for each Lucentis injection, versus $3 for each Avastin injection.
4. Avastin (Genentech) is the cheapest, at $50 per dose, compared with Lucentis (Genentech), at $2,000 per dose. Both are designed to be given monthly, or on an as-needed basis (stopping the injection if no fluid builds up in the eye.
5. Eyelea (Regeneron) became FDA-approved about six months ago. Eyelea is administered every 2 months at about $1800 per injection. Eyelea is potentially half as cheap as Lucentis.
The Avastin-Lucentis Data
Here’s my summary of the key findings at one year:
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 wet 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.
Safety Signal Fails to Materialize
Since the one-year data was released, industry has been pushing hard to press safety issues with Avastin. The one-year trial results made the cheaper Avastin look like a reasonable first-line drug choice.
An industry-sponsored safety analysis done in conjunction with Johns Hopkins researchers using Medicare claims data came out when the first-year NEI study data surfaced, showing an 11% higher mortality risk and 57% higher risk of cerebral hemorrhage in patients using Avastin. Even though Genentech pressed hard with the results, the results didn’t fly because the study was not able to ascertain other patient factors, including stroke, hypertension, and cardiovascular risks.
Notably, at two years, the trial investigators, the American Academy of Ophthalmology, and many other authorities concluded that both Avastin and Lucentis had strong efficacy. The AAO no longer describes differences in serious adverse events with the two drugs as worrisome. The investigators wrote: “There were no differences in rates of death or arteriothromotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab [Avastin] is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.”
The AAO press release lauded the study as “seminal” in “comparative effectiveness research,” a marked departure from AAO’s defensive stance at year one, when they stressed the importance of MD choice and autonomy.
Donald S. Fong, MD, MPH, Director of Clinical Trials Research, Kaiser Permanente Southern California, Pasadena, CA, told Patient POV: “As far as I am concerned, Avastin is first line. If it doesn’t work, I will go to Eyelea, which is half as expensive as Lucentis.”
There were a few isolated issues with compounding of Avastin and industry tried to use this as a lesson in going for brand.
Patients Need to Know More About Their Doctor
Patients would benefit from knowing a lot more about their eye doctors and all other doctors that just isn’t out there. In a previous article on Patient POV, Ricki Lewis told the story of a patient with osteogenesis imperfecta, a condition which has eye manifestations. Some ophthalmologists are unfamiliar with the disorder.
I don’t mean to single out ophthalmology. These issues are relevant to knowing all of your doctors. Why should journals be the only place where physician disclosures are mandated? Why can’t patients find reliable data on physician experience as well?
Clarification: The following was inadvertently left out of the original piece. Genentech has purposely not sought FDA approval for Avastin for the treatment of wet macular degeneration. Lucentis is a fragment of the Avastin.