Article Date: 1/1/2006

Macugen Being Widely Adopted by Retina Specialists
Survey also shows high interest in Avastin and Lucentis.
BY JERRY HELZNER, SENIOR EDITOR

About 2 out of 3 retina specialists who treat wet AMD have incorporated pegaptanib sodium (Macugen, OSI Pharmaceuticals/Pfizer) into their regular practice, but an even larger number believe they will be using ranibizumab (Lucentis, Genentech/Novartis) "and other antiangiogenics" in the future. Meanwhile, 19% of retina specialists who treat wet AMD are currently using the antiangiogenic cancer drug bevacizumab (Avastin, Genentech) off-label with at least some patients, and many more doctors are following use of the drug with interest. (Please see Genentech's position on off-label use of Avastin for wet AMD on page 17.)

These are the salient findings from a recent Retinal Physician survey that drew responses from a total of
100 retina specialists. The e-mailed survey was conducted in the fall of 2005 and consisted of questions designed to determine retina specialists' views on current and potential future treatments for wet AMD. One of the key aims of the survey was to determine what percentage of doctors are currently using off-label bevacizumab intravitreally and in what type of patients are they using this therapy, which was approved in 2004 as a treatment for colorectal cancer.

Several prominent retina specialists reviewed the survey results and were asked to comment on specific aspects of the survey. The following are the questions posed to them and their responses:

Q. Are you surprised at the percentage of retina specialists now using Macugen? Why or why not?

Philip Rosenfeld, MD, Miami: "Not at all surprised. It's approved for all lesion types."

George Williams, MD, Royal Oak, Mich: "I am surprised that only 67% of retina surgeons treating exudative AMD use Macugen. There is strong evidence that Macugen is the only proven therapy for large occult lesions and good vision. It is incumbent among retina surgeons to at least discuss the availability of Macugen with their patients."

Abdhish Bhavsar, MD, Minneapolis: "No, I would expect retina specialists to add this medicine to their armamentarium for managing CNV. However, it seems to be about as effective as PDT alone for most cases of CNV."

Leonard S. Kirsch, MD, FRCSC, Largo, Fla: "I'm using Macugen in close to 100% of my wet AMD patients, except for those who object to needles, some with purely classic lesions who respond well to PDT, and a few with small extrafoveal lesions who can be treated with a laser."

Q. While many of the responders are performing Macugen injections, the majority of those who are doing so are also continuing to use an equal ratio of other treatments (laser, PDT, PDT with Kenalog). How would you analyze this response?

Fareed Ali, MD, FRCSC, Mississauga, Ontario, Canada: "The most important item this shows is that very few retinal specialists are treating more than 50% of their exudative AMD patients with Macugen (see question 3 on page 62). So we would infer that at least half of all exudative AMD patients are receiving treatment other than Macugen. Only 2 treatments for wet AMD have been rigorously proven in formal FDA trials (ie: fulfilled study criteria without resorting to subgroup analysis): PDT (only for classic) and Macugen. Most wet AMD is nonclassic, so if we followed the trials rigorously, Macugen use should be much higher. So what this tells us is that as retinal specialists we are commonly using treatments that are not strictly FDA approved, ie: "off-label" to some extent. These treatments include PDT for nonclassic, Kenalog, Avastin, TTT, feeder vessel, and a few others, and combined they are used more than Macugen."

Dr. Williams: "The continuing use of other therapies for wet AMD is a reflection of the heterogeneity of the clinical manifestations of age-related macular degeneration as well as logistical issues associated with Macugen therapy. Clearly, there are some eyes that respond well to PDT, either with or without Kenalog. In addition, eyes with extrafoveal choroidal neovascularization can often do well with thermal laser ablation. At the present time, we have no available therapy that effectively treats all of the clinical manifestations of exudative AMD."

Q. The survey responses, as well as discussions during this year's Retina Society, show that many retinal specialists consider Avastin a viable solution to what is lacking in current therapies for exudative AMD. What are your thoughts on this and do you have any reservations about these high numbers of specialists who believe Avastin will replace current therapies for AMD?

Dr. Williams: "The enthusiasm for Avastin is driven by the fact that none of the other available treatments have demonstrated the ability to significantly improve visual function. The assumption is that Avastin will behave similarly to Lucentis. Although the preliminary experience is certainly compelling, we have no long-term data that demonstrates either the equivalence of Avastin with Lucentis or the safety of Avastin. In the absence of a confirmatory randomized head-to-head trial between Avastin and Lucentis, I would be reluctant to routinely use Avastin once Lucentis becomes available."

Dr. Rosenfeld: "Because of the growing use of Avastin, we must proceed with a prospective clinical trial and eventually our profession will demand a head-to-head comparison with Lucentis."

Dr. Bhavsar: "I am a conscientious objector to the use of Avastin. We know very little about the safety data for intravitreal use of Avastin and there was no attempt to obtain any safety data prior to some individuals advocating the widespread use of Avastin."

Dr. Kirsch: "I find the usage of Avastin for AMD alarmingly high. Avastin has not been studied for the eye. There may be issues with side effects. It should be looked at in the context of a clinical trial."

Q. What kind of impact will Avastin have on AMD treatment and research and development on new therapies?

Dr. Bhavsar: "Avastin may make it difficult to enroll patients in other trials for new treatments."

Dr. Ali: "One possible benefit of Avastin is it may stimulate companies to pursue completely new areas of AMD research aside from anti-VEGF and intravitreal drugs."

Q. What are your thoughts on the newer investigational therapies for AMD listed in question 10?

Dr. Bhavsar: "Of those listed, the only treatment that shows real promise at this time with minimal risks is Lucentis."

Dr. Williams: "Randomized controlled clinical trials have demonstrated the lack of efficacy for TTT, submacular surgery, and radiation therapy. There are no trials on retinal translocation. Select investigators have reported promising results. However, I think it is unlikely that this surgical approach will gain wide acceptance. The preliminary results with ranibizumab are very exciting and the future certainly seems to be with antiangiogenic therapy."

Dr. Ali: "TTT likely still has an important role given its safety, cost-effectiveness, and recent poor Visudyne (results) in Occult (VIO) trial results. Radiation and surgical therapies for wet AMD will likely be abandoned completely. New anti-VEGF will have to be superior in cost to Avastin and/or Lucentis in trial results. Feeder vessel still looks impractical due to the expertise and equipment needed."

Dr. Kirsch: "I'm a champion for my patients. I will look forward to whatever can help my patients."

Dr. Rosenfeld: "I'm always looking for treatments that will improve and maintain vision with fewer retreatments and that are safer and more cost-effective. That's not too much to ask, is it?"

AMD Treatment Preference Survey
(100 total responses to survey. Percentages for each question may not total 100% as not all responders answered all questions).

1. Do you treat patients with exudative AMD in your practice?

84% - Yes   16% - No

6. Aside from Macugen, what other AMD treatments are you currently using on at least some percentage of your patients? (Treatments listed in order of most used to least used)

1. PDT with triamcinolone (Kenalog)

2. PDT alone

3. PDT with Macugen

4. Laser photocoagulation

5. Other

2. If you DO treat patients with exudative AMD, do you currently perform Macugen injections?

67% - Yes   22% - No

7. Are you currently using Avastin in your practice?

19% - Yes   78% - No

3. If you DO perform Macugen injections, what percentage of your patients with exudative AMD receive Macugen injections?

7% - Fewer than 5%   7% - 50%-75%

23% - 5%-25%   7% - More than 75%

27% - 25%-50%

 

8. If you ARE using Avastin, how do you use it and for what type of patient?

   • Wet AMD with patients failing Macugen

   • I just started and I am still evaluating its application. Now I am using it for patients who do poorly with PDT and Macugen

   • Wet AMD

   • I'm using it on everyone who isn't already on Macugen and responding well to Macugen

   • Investigational agent

   • Same indications as Macugen

   • Intraocular injection for all wet AMD

   • Fibrovascular PED

   • CRVO, some AMD combination with PDT; some Avastin alone at 6-week to 2-month (intervals)

   • PDT and Macugen failures

   • Intravitreal exudative AMD

   • Decreased vision, leakage, PDT failure or PDT and Macugen failure

   • Rescue cases initially, but now use for all

   • As last resort

4. If you DO NOT now perform Macugen injections, do you plan to start performing Macugen injections in the future?

54.5% - Yes   40.9% - No

9. Do you see Avastin replacing one or more of the therapies that are currently used for exudative AMD?

58% - Yes   28% - No

5. If you DO NOT currently perform Macugen injections and DO NOT plan to perform Macugen injections, please explain why.

   � I do limited retina work

   � It does not work

   � Not approved by hospital

   � Elderly individuals don't view 16 injections over 2 years as enhancing their quality of life. And, oh yes, the drug appears marginally effective at best when used as approved

   � 1. Not helpful 2. Lucentis available starting soon 3. Avastin available now

   � The field is changing too rapidly. We have good retinal specialists who do a good job and keep up to date on the changes

   � Practice is consult only; retired from active hands-on treatment

   � Used to use it, but switched to Avastin because of increased efficacy

   � I think this treatment is better in the hands of a vitreoretinal surgeon who deals with all aspects of ARMD

   � I need to research this subject in detail before performing these procedures

10. Which experimental therapies for AMD are you likely to use in the future?

9% - Transpupillary thermotherapy

8% - Submacular surgery

4% - Radiation therapy

14% - Implantable miniaturized telescope

69% - Ranibizumab or another antiangiogenic therapy

5% - Retinal translocation

7% - Other:____________________________

_______________________________________

_______________________________________

_______________________________________

_______________________________________

_______________________________________

_______________________________________

_______________________________________



Retinal Physician, Issue: January 2006