Avastin and Lucentus Equal for Treating Age-Related
Macular Degeneration Says NIH Study
AMD is the leading cause of vision loss and
blindness in senior citizens
May 4, 2011 - Researchers are reporting results
from the first year of a two-year clinical trial that Avastin, a drug
approved to treat some cancers and that is commonly used off-label to
treat age-related macular degeneration (AMD), is as effective as the
Food and Drug Administration-approved drug Lucentis for the treatment of
AMD. AMD is the leading cause of vision loss and blindness in senior
citizens.
The report, from the Comparison of AMD Treatments
Trials (CATT), was published online in the New England Journal of
Medicine on Sunday, May 1, 2011. CATT is funded by the National Eye
Institute (NEI), a part of the National Institutes of Health.
"Over 250,000 patients are treated each year for
AMD, and a substantial number of them receive Avastin. Given the lack of
efficacy data regarding Avastin for AMD treatment, the NEI had an
obligation to patients and clinicians to conduct this study," said Paul
A. Sieving, M.D., Ph.D., director of the NEI.
In its advanced stages, the wet form of AMD spurs
the growth of abnormal blood vessels, which leak fluid and blood into
the macula and obscure vision. The macula is the central portion of the
retina that allows us to look straight ahead and to perceive fine visual
detail. Accumulation of fluid and blood damages the macula, causing loss
of central vision. AMD can severely impede mobility and independence.
Many patients are unable to drive, read, recognize faces or perform
tasks that require hand-eye coordination.
Genentech, the maker of both drugs, originally
developed Avastin to prevent blood vessel growth that enables cancerous
tumors to develop and spread. In 2004, the FDA approved Avastin for the
systemic treatment of metastatic colon cancer. Genentech later developed
Lucentis, derived from a protein similar to Avastin, specifically for
injection in the eye to block blood vessel growth in AMD.
In 2005, two Genentech-sponsored clinical trials
established Lucentis as highly effective for the treatment of wet AMD.
During the year between the announcement of the trial results and the
release of Lucentis, ophthalmologists began injecting AMD patients with
low doses of Avastin, due to its similarity to Lucentis and its
availability.
The FDA has not licensed Avastin for the treatment
of AMD.
Numerous physicians noted a beneficial treatment
effect and Avastin's use grew rapidly despite the lack of data on
safety, efficacy and dosing from randomized clinical trials to support
its use. Ophthalmologists used Avastin primarily as needed, or pro re
nata (PRN), when there was evidence of active disease.
The FDA approved Lucentis in 2006. However, most
clinicians adopted PRN dosing for Lucentis, which was a departure from
FDA-approved labeling and the monthly dosing schedule evaluated in the
Genentech-sponsored clinical trials. It was not known if PRN dosing
would produce the same long term vision benefits that were achieved with
monthly administration.
NEI launched CATT in 2008 to compare Lucentis and
Avastin for treatment of wet AMD. The study has now reported results for
1,185 patients treated at 43 clinical centers in the United States.
Patients were randomly assigned and treated with one of four regimens
for a year. They received Lucentis monthly or PRN, or Avastin monthly or
PRN. Enrollment criteria required that study participants had active
disease.
Patients in the monthly dosing groups received an
initial treatment and then had an injection every 28 days. Patients in
the PRN groups received an initial treatment and were then examined
every 28 days to determine medical need for additional treatment.
PRN
groups received subsequent treatment when there were signs of disease
activity, such as fluid in the retina. Ophthalmologists involved in
patient care did not know which study drug a patient was getting, to
make sure that the data was not affected by how anyone felt about the
treatment.
Change in visual acuity served as the primary
outcome measure for CATT. Thus far, visual acuity improvement was
virtually identical (within one letter difference on an eye chart) for
either drug when given monthly.
In addition, no difference was found in the
percentage of patients who had an important gain or loss in visual
function.
Also, when each drug was given on a PRN schedule,
there also was no difference (within one letter) between drugs. PRN
dosing required four to five fewer injections per year than monthly
treatment. Visual gains were about two letters less with PRN than with
monthly treatment but overall visual results were still excellent.
"In addition to the primary finding of equivalence
between Lucentis and Avastin for visual acuity, CATT also demonstrates
that PRN dosing is a viable treatment option for either of these drugs,"
said Daniel F. Martin M.D., study chair for CATT and chairman of the
Cole Eye Institute at the Cleveland Clinic. "Substantial visual acuity
gains may be accomplished with a lower treatment burden."
Adverse events indicate development or worsening of
a medical condition. They may or may not be causally associated with the
clinical trial treatment, but they are always monitored and reported in
any clinical trial.
The median age of patients in CATT was over 80
years, and a high rate of hospitalizations might be anticipated as a
result of chronic or acute medical conditions more common to older
populations.
Serious adverse events (primarily hospitalizations)
occurred at a 24 percent rate for patients receiving Avastin and a 19
percent rate for patients receiving Lucentis. These events were
distributed across many different conditions, most of which were not
associated with Avastin in cancer clinical trials where the drug was
administered at 500 times the dose used for AMD.
The number of deaths, heart attacks, and strokes
were low and similar for both drugs during the study. CATT was not
capable of determining whether there is an association between a
particular adverse event and treatment. Differences in serious adverse
event rates require further study.
Investigators in the CATT study will continue to
follow patients through a second year of treatment. These additional
data will provide information on longer-term effects of the drugs on
vision and safety.
The FDA has not evaluated the data from the CATT
trial.
The National Eye Institute, part of the National
Institutes of Health, leads the federal government's research on the
visual system and eye diseases. NEI supports basic and clinical science
programs that result in the development of sight-saving treatments. For
more information, visit
www.nei.nih.gov
About the National Institutes of Health (NIH): NIH,
the nation's medical research agency, includes 27 Institutes and Centers
and is a component of the U.S. Department of Health and Human Services.
NIH is the primary federal agency conducting and supporting basic,
clinical, and translational medical research, and is investigating the
causes, treatments, and cures for both common and rare diseases. For
more information about NIH and its programs, visit
www.nih.gov.
About Macular Degeneration
Also
called: Age-related macular degeneration, AMD
Macular degeneration, or age-related macular degeneration (AMD) is a
leading cause of vision loss in Americans 60 and older. It is a disease
that destroys your sharp, central vision. You need central vision to see
objects clearly and to do tasks such as reading and driving.
AMD
affects the macula, the part of the eye that allows you to see fine
detail. It does not hurt, but it causes cells in the macula to die. In
some cases, AMD advances so slowly that people notice little change in
their vision. In others, the disease progresses faster and may lead to a
loss of vision in both eyes. Regular comprehensive eye exams can detect
macular degeneration before the disease causes vision loss. Treatment
can slow vision loss. It does not restore vision.
May 4, 2011 - Researchers are reporting results
from the first year of a two-year clinical trial that Avastin, a drug
approved to treat some cancers and that is commonly used off-label to
treat age-related macular degeneration (AMD), is as effective as the
Food and Drug Administration-approved drug Lucentis for the treatment of
AMD. AMD is the leading cause of vision loss and blindness in senior
citizens.