BUSINESS WIRE
Gains in visual acuity achieved in initial 12-week fixed dosing phase
of study maintained in PRN (as-needed) dosing phase
TARRYTOWN, N.Y. & LEVERKUSEN, Germany--(BUSINESS WIRE)--Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN) and Bayer
HealthCare AG today announced that VEGF Trap-Eye dosed on a PRN
(as-needed) dosing schedule maintained the statistically significant
gain in visual acuity achieved after an initial, 12-week, fixed-dosing
phase of a Phase 2 study in the neovascular form of Age-related Macular
Degeneration (wet AMD). A full analysis of the 32-week results of the
Phase 2 study will be presented today at the 2008 Association for
Research in Vision and Ophthalmology (ARVO) meeting in Fort Lauderdale,
Florida. The data being reported at the meeting are available on the
Regeneron website (www.regeneron.com
on the Investor Relations page, under the Presentations heading).
Study results showed that across all dose groups in the study
population, the 6.6 mean letter gain in visual acuity achieved versus
baseline at the week 16 evaluation visit, following 12 weeks of fixed
dosing, was maintained out to week 32 (a 6.7 mean letter gain versus
baseline; p< 0.0001) using a PRN
dosing schedule (where dosing frequency was determined by the physician’s
assessment of pre-specified criteria). The decrease in retinal
thickness, an anatomical measure of treatment effect achieved with a
fixed-dose schedule was also maintained for all dose groups combined at
week 32 (a 137 micron mean decrease versus baseline, p<0.0001).
In this double-masked, prospective, randomized, multi-center Phase 2
trial, 157 patients were randomized to five dose groups and treated with
VEGF Trap-Eye in one eye. Two groups initially received monthly doses of
0.5 or 2.0 milligrams (mg) of VEGF Trap-Eye for 12 weeks and three
groups received quarterly doses of 0.5, 2.0, or 4.0 mg of VEGF Trap-Eye
(at baseline and week 12). Following the initial 12-week fixed-dose
phase of the trial, patients continued to receive therapy at the same
dose on a PRN dosing schedule based upon the physician assessment of the
need for re-treatment in accordance with pre-specified criteria.
Patients were monitored for safety, retinal thickness, and visual
acuity. These data represent the week 32 analysis from the 52-week
study, which is continuing to follow patients.
Patients receiving monthly doses of VEGF Trap-Eye, either 0.5 or 2.0 mg,
for 12 weeks followed by PRN dosing thereafter achieved mean
improvements in visual acuity of 8.0 (p<0.01
versus baseline) and 10.1 letters (p<0.0001
versus baseline), respectively, and mean decreases in retinal thickness
of 141 (p<0.0001 versus baseline)
and 162 microns (p<0.0001 versus
baseline) at week 32, respectively. While PRN dosing also maintained the
improvements in retinal thickness and visual acuity achieved versus
baseline following a fixed dosing regimen utilizing quarterly dosing at
baseline and week 12, the results achieved with a quarterly fixed dosing
regimen were generally not as robust as obtained with initial fixed
monthly dosing.
VEGF Trap-Eye was generally safe and well tolerated and there were no
drug-related serious adverse events. There was one reported case of
culture-negative endophthalmitis/uveitis in the study eye, which was
deemed not to be drug-related. The most common adverse events were those
typically associated with intravitreal injections.
After the last fixed-dose administration at week 12, patients from all
dose groups combined required, on average, only one additional injection
over the following 20 weeks to maintain the visual acuity gain
established during the fixed-dosing period. Notably, 55 percent of the
patients who received 2.0 mg monthly for 12 weeks did not require any
additional treatment throughout the next 20-week PRN dosing period.
Moreover, 97 percent of the patients who received 2.0 mg monthly for 12
weeks did not require re-dosing at the week 16 evaluation visit,
indicating that an 8-week dosing schedule may be feasible.
“Due to its high affinity for all isoforms of
VEGF-A and PlGF, potent mediators of blood vessel overgrowth in wet AMD,
as well as its long residence time in the eye, it is anticipated that
VEGF Trap-Eye may be able to be dosed at a frequency less than once
monthly, especially on a chronic basis, without compromising visual
acuity,” stated Quan Dong Nguyen, M.D.,
M.Sc.,* Assistant Professor of Ophthalmology, Wilmer Ophthalmological
Institute, the Johns Hopkins University School of Medicine, Baltimore,
MD and a primary investigator in the Phase 2 study. “These
emerging Phase 2 clinical data seem to support the concept of durability
of VEGF Trap-Eye.”
In this study, treatment with VEGF Trap-Eye was associated with a
reduction in the size of the choroidal neovascular membrane (CNV), the
lesion that is the underlying cause of vision loss due to wet AMD.
Patients initially treated with a 0.5 mg or 2.0 mg monthly fixed dose
for 12 weeks, followed by PRN dosing thereafter, experienced 1.55 mm2
and 2.52 mm2 reductions in mean CNV size at 24
weeks (the most recently available analysis from the independent reading
center) versus baseline, respectively. Patients treated initially with
fixed quarterly dosing also experienced an overall reduction in CNV size.
“Regression in CNV size is generally not seen
when treating wet AMD patients. The reduction in CNV size achieved thus
far with VEGF Trap-Eye treatment highlights the potential clinical
utility of this investigational treatment in patients suffering from
this devastating condition,” stated Jason
Slakter, M.D., Clinical Professor of Ophthalmology, New York University
School of Medicine, New York.
"These study results further increase our confidence in the design of
our Phase 3 clinical program for VEGF Trap-Eye in wet AMD," said George
D. Yancopoulos, M.D., Ph.D., President of Regeneron Research
Laboratories. "These studies are evaluating the clinical efficacy and
safety of VEGF Trap-Eye, using a monthly loading dose of 0.5 mg or 2.0
mg for 12 weeks, followed by a nine-month fixed-dosing regimen of 0.5 mg
monthly, 2.0 mg monthly, or 2.0 mg every eight weeks. In the second year
of the studies, all patients will be dosed on a PRN basis."
About the Phase 3 Program in Wet AMD
Regeneron and Bayer HealthCare initiated a Phase 3 global development
program for VEGF Trap-Eye in wet AMD in August 2007. In two Phase 3
trials, the companies are evaluating VEGF Trap-Eye using four- and
eight-week dosing intervals in direct comparison with ranibizumab
(Lucentis®, a
registered trademark of Genentech, Inc.) administered every four weeks
according to its label during the first year of the studies. PRN dosing
will be evaluated during the second year of each study. The VIEW1 study
is currently enrolling patients in the United States and Canada. The
VIEW2 study has recently been initiated and will enroll patients in up
to 200 centers in Europe, Asia Pacific, Japan, and Latin America. The
companies are collaborating on the global development of VEGF Trap-Eye
for the treatment of wet AMD, diabetic eye diseases, and other eye
diseases and disorders. Bayer HealthCare will market VEGF Trap-Eye
outside the United States, where the companies will share equally in
profits from any future sales of VEGF Trap-Eye. Regeneron maintains
exclusive rights to VEGF Trap-Eye in the United States.
About VEGF Trap-Eye
Vascular Endothelial Growth Factor (VEGF) is a naturally occurring
protein in the body whose normal role is to trigger formation of new
blood vessels (angiogenesis) to support the growth of the body's tissues
and organs. It has also been associated with the abnormal growth and
fragility of new blood vessels in the eye, which lead to the development
of wet AMD. The VEGF Trap-Eye is a fully human, soluble VEGF receptor
fusion protein that binds all forms of VEGF-A along with the related
Placental Growth Factor (PlGF). VEGF Trap-Eye is a specific and highly
potent blocker of these growth factors. Blockade of VEGF, which can
prevent abnormal blood vessel formation and vascular leak, has proven
beneficial in the treatment of wet AMD and a VEGF inhibitor,
ranibizumab, has been approved for treatment of patients with this
condition.
About Wet AMD
Age-related Macular Degeneration (AMD) is a leading cause of acquired
blindness. Macular degeneration is diagnosed as either dry
(nonexudative) or wet (exudative). In wet AMD, new blood vessels grow
beneath the retina and leak blood and fluid. This leakage causes
disruption and dysfunction of the retina creating blind spots in central
vision, and it can account for blindness in wet AMD patients. Wet AMD is
the leading cause of blindness for people over the age of 65 in the U.S.
and Europe.
About Regeneron Pharmaceuticals, Inc.
Regeneron is a fully integrated biopharmaceutical company that
discovers, develops, and commercializes medicines for the treatment of
serious medical conditions. In addition to ARCALYST™
(rilonacept) Injection for Subcutaneous Use, its first commercialized
product, Regeneron has therapeutic candidates in clinical trials for the
potential treatment of cancer, eye diseases, and inflammatory diseases,
and has preclinical programs in other diseases and disorders. Additional
information about Regeneron and recent news releases are available on
Regeneron's web site at www.regeneron.com.
Forward Looking Statement
This news release discusses historical information and includes
forward-looking statements about Regeneron and its products, development
programs, finances, and business, all of which involve a number of risks
and uncertainties, such as risks associated with preclinical and
clinical development of Regeneron’s drug
candidates, determinations by regulatory and administrative governmental
authorities which may delay or restrict Regeneron’s
ability to continue to develop or commercialize its product and drug
candidates, competing drugs that are superior to Regeneron’s
product and drug candidates, uncertainty of market acceptance of
Regeneron’s product and drug candidates,
unanticipated expenses, the availability and cost of capital, the costs
of developing, producing, and selling products, the potential for any
collaboration agreement, including Regeneron’s
agreements with the sanofi-aventis Group and Bayer HealthCare, to be
canceled or to terminate without any product success, risks associated
with third party intellectual property, and other material risks. A
more complete description of these and other material risks can be found
in Regeneron's filings with the United States Securities and Exchange
Commission (SEC), including its Form 10-K for the year ended December
31, 2007. Regeneron does not undertake any obligation to update
publicly any forward-looking statement, whether as a result of new
information, future events, or otherwise unless required by law.
* The assessment made by Dr. Nguyen does not necessarily imply
endorsement by the Johns Hopkins University, the Johns Hopkins Hospital,
or the Johns Hopkins Medical Institutions.