Macugen Being Widely Adopted by Retina Specialists
Survey also shows high interest in Avastin
HELZNER, SENIOR EDITOR
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
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
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
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."
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?"
Treatment Preference Survey
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?
Yes 16% - No
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
1. PDT with
2. PDT alone
3. PDT with Macugen
4. Laser photocoagulation
you DO treat patients with exudative AMD, do you currently perform Macugen
67% - Yes 22% -
you currently using Avastin in your practice?
19% - Yes 78%
you DO perform Macugen injections, what percentage of your patients with
exudative AMD receive Macugen injections?
7% - Fewer than 5% 7%
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
I just started and I am still evaluating
its application. Now I am using it for patients who do poorly with PDT and Macugen
I'm using it on everyone who isn't already
on Macugen and responding well to Macugen
Same indications as Macugen
Intraocular injection for all wet AMD
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
As last resort
you DO NOT now perform Macugen injections, do you plan to start performing
Macugen injections in the future?
54.5% - Yes 40.9%
9. Do you see Avastin replacing one or more of
the therapies that are currently used for exudative AMD?
58% - Yes 28% -
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
� 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
5% - Retinal translocation
7% - Other:____________________________
Retinal Physician, Issue: January 2006