Welcome to the premier issue of AMD Update!
It is estimated that 15 million people in the United States have age-related macular degeneration (AMD), with more than 1.75 million having advanced disease (defined as neovascular AMD or geographic atrophy); the number with advanced disease is expected to climb to almost 3 million by the year 2020. AMD is the leading cause of blindness in adults over 55 years of age.
AMD Update is a
monthly e-newsletter dedicated to bringing to the
ophthalmologist the latest and most useful clinical information
and literature reviews on the management of AMD in a quick, easy
to review format. The articles will be written by a
variety of authors in order to draw upon a wealth of expertise.
I am pleased to serve as Editor of AMD Update. I hope
that you will find the information timely and applicable to your
practice, and that you will look forward to each issue.
Scott, MD, MPH
Professor of Ophthalmology and Health
Penn State College of Medicine
Lucentis and Avastin: When to Use Which?
By: Robert Avery, MD
California Retina Consultants, Santa Barbara, CA
drugs have ever gained market-share, acceptance, and even
enthusiastic use as rapidly as intravitreal Avastin has over the
past year. This feat is particularly remarkable since its use is
strictly “off-label”. One reason for Avastin’s rapid
acceptance is its apparent similarity to Lucentis. By the
time most people heard of intravitreal Avastin, the 1 year
Marina results had been presented showing that Lucentis provided
a dramatic efficacy improvement over the standard of care, and
there was quite a “buzz” about the potential for anti-VEGF
therapy. However, because Lucentis would not be available
for at least a year, and patients and doctors did not want to
wait for FDA approval if a similar treatment were available,
many retina specialists started offering intravitreal Avastin.
Now, over a year later, we have significantly more experience
with Avastin, and we also have the FDA approval of Lucentis;
hence the dilemma as to which drug to use.
The case for
Lucentis is formidable. Multiple phase III randomized
controlled clinical trials evaluating its use in neovascular AMD
have shown a striking efficacy benefit over the previous
standard of care, with a good safety profile.1,2
On the other hand, many more patients worldwide have now been
treated with Avastin than Lucentis. There are multiple
published series of Avastin for AMD that demonstrate an anatomic
and visual effect similar to that seen with Lucentis; however,
most of these studies are short term, retrospective,
uncontrolled and lack the standardized vision measurements and
safety reporting required in FDA trials.3-9
Theoretically, the significantly longer serum half-life of
Avastin compared to Lucentis could increase its risk of systemic
complications. On the other hand, the intravitreal dose of
Avastin is several orders of magnitude less than what is used
intravenously in cancer patients. Finally, the intravitreal
half-life of Avastin may be significantly longer than that of
Lucentis and allow for less frequent injections. In
primates, a Genentech study found an intravitreal half-life of
5.6 days for a full-length humanized monoclonal antibody similar
to Avastin and 3.2 days for a Fab fragment similar to Lucentis.10
Many clinicians currently use Avastin every 6 to 8 weeks, while
Lucentis is approved for use every 4 weeks.
important difference between Avastin and Lucentis is the cost of
the drugs. Medicare in most states covers Avastin, and the
reimbursement varies from carrier to carrier. In many states,
Medicare allows $57 for one unit of Avastin. The allowable
for Lucentis is $2,067. To Genentech’s credit, the company
has developed a program to facilitate access to Lucentis for
those who cannot afford it.
So which agent
do we offer to our patients? Interestingly, in a recent
survey of members of the American Society of Retina Specialists,
the 389 responders were about equally split between Avastin and
Lucentis when choosing a drug for neovascular AMD.11
I offer patients both drugs with a detailed explanation of the
potential advantages and disadvantages of each. For some
patients, the proven safety and efficacy of Lucentis overrides
the cost concern, and for others, Avastin has worked very well
for them for over a year and they see no reason to change.
For indications other than AMD, Lucentis is not typically
covered, and Avastin is usually selected. For patients
with a significant, recent thromboembolic history, Avastin is
rarely selected because of potential safety and medicolegal
issues, and Lucentis is offered cautiously. Fortunately,
the NIH has agreed to sponsor a head to head trial of Avastin
and Lucentis to help our patients and physicians decide which
drug to use.
Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, et al.
neovascular age-related macular degeneration. N Engl J Med
2006 Oct 5;355(14):1419-31.
2. Brown DM, Kaiser PK,
Michels M, Soubrane G, et al. Ranibizumab versus
verteporfin for neovascular age-related macular degeneration.
N Engl J Med 2006 Oct 5;355(14):1432-44.
Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA,
bevacizumab (Avastin) for neovascular age-related macular
degeneration. Ophthalmology 2006 Mar;113(3):363-372.e5.
Laud K, Fine HF, Klancnik JM Jr, Meyerle CB, Yannuzzi LA,
Sorenson J, Slakter J, Fisher YL, Cooney MJ. Intravitreal
bevacizumab treatment of choroidal neovascularization secondary
to age-related macular degeneration. Retina 2006
5. Rich RM, Rosenfeld PJ, Puliafito
CA, Dubovy SR, Davis JL, Flynn HW Jr, Gonzalez S, Feuer WJ, Lin
RC, Lalwani GA, Nguyen JK, Kumar G. Short-term safety and
efficacy of intravitreal bevacizumab (Avastin) for neovascular
age-related macular degeneration.
Retina 2006 May-Jun;26(5):495-511.
6. Ladewig MS,
Ziemssen F, Jaissle G, Helb HM, Scholl HP, Eter N, Bartz-Schmidt
KU, Holz FG. Intravitreal bevacizumab for
neovascular age-related macular degeneration.
Ophthalmologe 2006 Jun;103(6):463-70.
7. Bashshur ZF,
Bazarbachi A, Schakal A, Haddad ZA, El Haibi CP, Noureddin BN.
Intravitreal bevacizumab for the management of choroidal
neovascularization in age-related macular degeneration.
Ophthalmol 2006 Jul;142(1):1-9.
RA, Jorge R, Calucci D, Cardillo JA, Melo LA Jr, Scott IU.
Intravitreal bevacizumab for choroidal neovascularization caused
by AMD (IBeNA Study): results of a phase 1 dose-escalation
Invest Ophthalmol Vis Sci 2006 Oct;47(10):4569-78.
Abraham-Marin ML, Cortes-Luna CF, Alvarez-Rivera G,
Hernandez-Rojas M, Quiroz-Mercado H, Morales-Canton V.
Intravitreal bevacizumab therapy for neovascular age-related
macular degeneration: a pilot study. Graefes Arch Clin Exp
Ophthalmol 2006 Sep 28; [Epub ahead of print]
Mordenti J, Cuthbertson RA, Ferrara N, et al.
Comparisons of the intraocular tissue distribution,
pharmacokinetics, and safety of 125I-labeled full-length and Fab
antibodies in rhesus monkeys following intravitreal
administration. Toxicol Pathol 1999;27:536–544.
and Trends (PAT) Survey. Presented at the American Society
of Retina Specialists. Cannes, Sept 2006.