Sunday, June 03, 2012

Avastin/Lucentis Update 52: Another Point of View

As you know, I have been writing about Avastin and the Avastin vs. Lucentis controversy since January 2006. There are now over 50 postings on this subject, and an additional 35 or so on various treatments for AMD, including the Comparisons of Age-Related Macular Degeneration Treatments Trials (the CATT Study). From time to time, as I’ve run across articles or blogs by others pertinent to these subjects, I’ve gotten in touch with the authors and requested permission to reproduce their words here. This is such an instance.

I recently was referred to a blog posting by Laura Newman on her Patient Point of View (POV) blog. It deals with the Avastin vs. Lucentis (and now Eylea from Regeneron) controversy, but more importantly, it asks patients with wet AMD to think about the potential biases that their eye doctor might have as to which drug treatment he/she would recommend.

I thought that Laura’s POV blog might be of interest to my audience and got in touch with her and asked for her permission to reproduce the writeup in this space.

She graciously said yes, and here it is:

Posted on May 22, 2012 by Laura Newman

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, Eylea, by Regeneron. 

Your Ophthalmologist’s Biases

Doctors talk about patient-centered care and 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 involvement 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?

Five Fast Facts on Wet Macular Degeneration Drugs

1. Currently, there are 3 drugs available demonstrated to improve vision: Avastin, Lucentis, and Eylea.

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. Eylea (Regeneron) became FDA-approved about six months ago. Eylea is administered every 2 months at about $1800 per injection. Eylea is potentially half as expensive as Lucentis.

The Avastin-Lucentis Data

Here's my summary of the key findings at one year:

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 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% of patients for patients on Avastin, compared with 19% 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. Differences in serious adverse events with the two drugs was no longer interpreted as worrisome. The investigators wrote: "There were no differences in rates of death or atherothrombotic 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 Eylea, 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 (brittle bone disease), 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 your doctor.  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.

Laura Newman Bio

Laura is a medical journalist and blogger. Her stories have appeared in peer-reviewed journals and on the web. She has covered ophthalmology as a reporter for several years, with both  Ophthalmology Times and Ocular Surgery News. She has also written news for Scientific American, The Lancet, and the Journal of the National Cancer Institute.

In Patient POV, she strives to bring the same rigor to telling stories about patients that she has shown in her previous work, which has featured research scientists and physicians.

Laura can be found on Twitter as: @lauramanny

Her email address is: Laura Newman


At 4:19 AM, Blogger rahul said...

Thanks for great information you write it very clean. I am very lucky to get this tips from you.

Eye Clinic Glasgow

At 5:52 PM, Anonymous Anonymous said...

Laura, great info on the drugs. But in the world of treatments for AMD they can only do so much!.
The unfortunate secret for better visual results, from any of these drugs is the time they are started. We have a cumbersome referral process which doesn't deliver the patient to the treating retina specialist early enough. I left a great job to take another in an area that focuses on improving the referring process. I saw first hand the struggles doctors had trying to save the vision in the first eye with my product Visudyne and although today's drugs are better, the referral process has not! We spend 1.5 billion to get 35-47% of patients to near normal vision because they got to the office with full blown CNV. Modern medicine has given us a great break in genetic testing to determine high risk patients and to monitor them more closely and it's only slowly being adopted. Check out Macula Risk and the simple cheek swab that can make a biig difference in getting high risk patients to the treating doctor when they are basically asumptomatic (. 20/50) with just a little su retinal fluid and a great chance to be treated early and even improve vision.
Early detection, early treatment= better visual acuity.
It's common sense, great science!


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