Retinal Specialist on the Avastin®/Lucentis® Controversy

    By Kevin E. Noonan

Earlier this week, the National Eye Institutes (NEI) of the National Institutes of Health announced that it would conduct a study comparing the effectiveness of two Genentech drugs, Lucentis® and Avastin®, for the treatment of age-related macular degeneration (AMD).  This was not good news for Genentech, because although treating AMD with Avastin® is an off-label use (Avastin® is approved for treating colon and certain lung cancers), the cost of the treatment is between 1% and 3% of the cost of Lucentis® treatment ($20-60 per dose versus $2,000/dose).

Lucentis® has been a great success for Genentech despite its cost, because it is one of only two FDA approved drugs for treating neovascular or "wet" AMD, a condition that if untreated leads inexorably to blindness.  The drug has been so successful that it has the lion's share of the market over Macugen (sold by EyeTech).  The drug has not been without controversy, however, since it is not a cure for AMD but merely stablizes the wet form, and in many patients prevents the condition from worsening.  This means that 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. is greater than $10 billion per year.  According to Dr. Edward Chaum, Plough Foundation Professor of Ophthalmology, University of Tennessee, this is more than the entire Medicare budget for all of ophthalmology (cataracts, diabetes, glaucoma, and everything else) combined.

Avastin® is so much cheaper because it is priced at $600/vial for intravenous use, but is injected into the eye at such small doses (0.1cc) that each vial can deliver 30 doses ($20/dose), says Dr. Chaum.  Genentech has opposed the off-label use of Avastin®, and cautioned ophthalmologists that there is a greater risk of stroke using Avastin.  However, the increased stroke risk was seen at the therapeutic dose for cancer patients, which is 400-fold higher than the dose used to treat AMD.  Recently, Genentech also reported that certain doses of Lucentis used for AMD are also associated with an increased risk of stroke.

Not surprisingly, Genentech's behavior has angered the Retina ophthalmology community, which has generally ignored Genentech's warnings and has been widely using Avastin® for AMD.  The results of the NEI study will not be available for about a year, but the situation should be clarified sooner than that, in view of anecdotal evidence from such off-label use and the expected disclosure of preliminary results.

Dr. Chaum and others believe that the results of the head-to-head clinical trial will likely validate use of Avastin® as being at least equivalent to Lucentis®.  If confirmed, Genentech will be forced to choose between removing Avastin® from the marketplace (which is unlikely, since it is a $2 billion/ year drug for cancer indications), or acquiescing to providing the drug in the lower dose amounts that are now provided only by compounding pharmacies.

The hard reality is that AMD is a progressive disease whose best treatment is prevention.  It is an indication of the dire consequences of AMD (blindness in old age) that patients and their physicians endure the therapeutic regimen (direct injection into the eye every 4-6 weeks) for drugs that at best only slow disease progression.  Genentech lost an opportunity with Avastin® and Lucentis® to solidify ties with a large and growing patient population and their doctors.  Perhaps their cooperation, if forthcoming, in the face of the expected equivalence results for these two drugs, and the resulting greater affordability for the majority of patients, can repair the damage.

Comments

[Irv Arons]

Readers interested in this subject might also be interested in taking a look at my web Journal. Since January 2006, I have been following and writing about Avastin and Lucentis, most recently reporting on the February 22nd front page story about these drugs appearing in the WSJ.

Prior to that, I posted a White Paper about the controversy, written by a group of retinal specialists (identified at the end of the piece). In all, I have now posted 13 stories about Avastin and Avastin vs Lucentis.

Please see my web Journal at:

http://irvaronsjournal.blogspot.com

Irv Arons

[Michael]

Here is a great audio interview with the director of health policy at the American Academy of Opthalmology on the head to head trial of Lucentis vs. Avastin:

http://health.scribemedia.org/2007/03/03/lucentis-avastin/

[Mya Wallace]

My father has wet ALMG and Dry ALMG. In the absence of treatmetn he was discharged 4 years ago and is now blind in one eye but has recently been re-admitted to consider treatment for his other eye with Dry ALMG now showing signs of the WET condtion. He is now being considered to retain his reamining sight with Lucentis on NHS which looks unlikely - If this fails where can I obtain for him treatment with Avastin

[barbara from NJ]

I was diagnosed with dry macular in Nov. and taking eye vitamins daily but this week having trouble seeing clocks and even reading large print books. Dr. exam shows bleeding in one eye and scheduled injections.I have to dedide avastin or lucentis. please tell me if its possible to change from dry to wet/

[Nurlan Uranayev]

My diagnose was and still is AMD wet form, 1 month ago i agreed to make injection of avastin. My current doctors were recommending me to make the second injection of Avastin at the end of October, but i am really afraid that it'd not help me and therefore i am planning to show my eyes to alternative clinic, which primary treatment of AMD is Lucentis. I heard that Lucentis is better and more effective to use after injection of Avastin (Munich-base study). Did somebody provide an injection of Lucentis after provision of injection of avastin? I'd really appreciate for any feedback.

[Pat P]

How does one prevent dry macular degeneration becoming wet?

[Kevin E. Noonan]

Dear Pat:

First, a disclaimer: while we are the Patent Docs, none of us are medical doctors or ophthamologists, so whatever you read here should not be used in lieu of speaking with a doctor if you are having vision problems.

But in an effort to be helpful, here is the definition of "wet" and "dry" macular degeneration from wikipedia.com:

The inner layer of the eye is the retina, which contains nerves that communicate sight, and behind the retina is the choroid, which contains the blood supply to the retina. In the dry (nonexudative) form, cellular debris called drusen accumulate between the retina and the choroid, and the retina can become detached. In the wet (exudative) form, which is more severe, blood vessels grow up from the choroid behind the retina, and the retina can also become detached. It can be treated with laser coagulation, and with medication that stops and sometimes reverses the growth of blood vessels.[1][2]

You might also look at the Amnerican Macular Degeneration Foundation website at www.macular.org.

Hope this helps.

[Ed Schlitt]

I have had 25 injections of Avastin for wet type, and my retina specialist is considering an every 4 week trial of Avastin for 4 treatments, then 4 of Lucentis, to see if an impprovement shows. I must say that the Avastin did curb the progression, and now hope an even better improvement with this trial.