PDF / 72 KB 
collectBayerNews_20080428_0182_en.pdf BayerNews_20080428_0182_en.pdf
Gains in visual acuity achieved in initial 12-week fixed dosing phase of study maintained in PRN (as-needed) dosing phase
Leverkusen, Germany and Tarrytown, NY, April 28, 2008 - Bayer HealthCare AG and
development partner Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN) 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 additional results underline that VEGF Trap-Eye has the potential to
significantly reduce retinal thickness and improve vision," said Dr. Gunnar
Riemann, member of Bayer HealthCare's Executive Committee. "The further
development of this compound is important for millions of people worldwide, who
suffer from this devastating ocular disease."
About the Phase 3 Program in Wet AMD
Bayer HealthCare and Regeneron 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 Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of
health care, nutrition and high-tech materials. Bayer HealthCare, a subsidiary
of Bayer AG, is one of the world's leading, innovative companies in the
healthcare and medical products industry and is based in Leverkusen, Germany.
The company combines the global activities of the Animal Health, Consumer Care,
Diabetes Care and Pharmaceuticals divisions. The pharmaceuticals business
operates under the name Bayer Schering Pharma AG. Bayer HealthCare's aim is to
discover and manufacture products that will improve human and animal health
worldwide. Find more information at www.bayerhealthcare.com.
About Bayer Schering Pharma
Bayer Schering Pharma is a worldwide leading specialty pharmaceutical company.
Its research and business activities are focused on the following areas:
Diagnostic Imaging, Hematology/Cardiology, Oncology, Primary Care, Specialized
Therapeutics and Women's Healthcare. With innovative products, Bayer Schering
Pharma aims for leading positions in specialized markets worldwide. Using new
ideas, Bayer Schering Pharma aims to make a contribution to medical progress
and strives to improve the quality of life. Find more information at
www.bayerscheringpharma.de.
