Genentech, Inc. (NYSE: DNA)
announced today positive one-year results from its second pivotal Phase III
study of the investigational drug Lucentis(TM) (ranibizumab) in patients with
wet age-related macular degeneration (AMD). Data from the ANCHOR study
comparing Lucentis to verteporfin (Visudyne(R)) photodynamic therapy (PDT)
showed a difference in mean change in visual acuity of 18 letters for patients
treated with 0.3 mg of Lucentis and 21 letters for patients treated with 0.5
mg of Lucentis from study entry compared to those treated with PDT at 12
months.
In the first year of this two-year study, patients treated with
Lucentis gained an average of 8.5 letters in the 0.3 mg dose group and 11
letters in the 0.5 mg dose group compared to patients treated with PDT, who
lost an average of 9.5 letters. In November 2005, Genentech announced that the
Phase III ANCHOR study met its primary efficacy endpoint of maintaining vision
(defined as a loss of less than 15 letters in visual acuity) in patients with
wet AMD. One-year data from the ANCHOR study were presented today during
Macula 2006, a medical symposium held in New York and sponsored by the
Manhattan Eye, Ear & Throat Hospital.
“Lucentis is the first investigational therapy that has shown improved
vision, not just a slowing of vision loss, in patients with all types of wet
AMD,” said Peter K. Kaiser, M.D., director, Clinical Research Center, The
Cleveland Clinic Cole Eye Institute, who presented the data today. “As a
result, physicians may be one step closer to being able to set a new
expectation for the future treatment of this condition.”
An analysis of the one-year data showed that adverse events were similar
to those seen in earlier trials of Lucentis. Common ocular adverse side
effects that occurred more frequently in the Lucentis arms than in the control
group were mild to moderate and included conjuctival hemorrhage, increased
intraocular pressure, eye pain and vitreous floaters. Serious ocular adverse
events that occurred more frequently in the Lucentis-treated arms were
uncommon and included endophthalmitis and intraocular inflammation (each
reported in less than 1 percent of patients per group). Among non-ocular
serious adverse events, the frequency of cerebral vascular events was less
than 1 percent of patients per group. The frequency of myocardial infarctions
was slightly higher in patients treated with 0.5 mg of Lucentis (2.1 percent)
than in the other two arms (0.7 percent).
Additional key clinically meaningful study findings include:
— 94 percent of patients (132/140) treated with 0.3 mg of Lucentis and
96 percent (134/139) of those treated with 0.5 mg of Lucentis lost
fewer than 15 letters compared to baseline, the primary efficacy
endpoint of the study, compared with 64 percent (92/143) of those
treated with PDT [p
— Nearly 36 percent of patients (50/140) treated with 0.3 mg of Lucentis
and 40 percent of patients (56/139) treated with 0.5 mg of Lucentis
improved vision by a gain of 15 letters or more compared with
approximately 6 percent of patients (8/143) treated with PDT.
— 31 percent of patients (44/140) treated with 0.3 mg of Lucentis and
nearly 39 percent of patients (54/140) treated with 0.5 mg of Lucentis
achieved visual acuity of 20/40 or better at 12 months compared with
approximately 3 percent (4/143) of those treated with PDT.
“Through the extensive clinical study program for Lucentis we have now
shown a significant improvement in vision compared to Visudyne and in patients
with all types of wet AMD,” said Hal Barron, Genentech senior vice president,
Development and chief medical officer. “We look forward to working with the
FDA on our BLA submission and Priority Review request. Given the existing
unmet medical need for patients with wet AMD, we are providing access to
Lucentis for eligible patients through SAILOR, a Phase IIIb safety study.”
In December 2005, Genentech announced that it had submitted a Biologics
License Application (BLA) to the U.S. Food and Drug Administration (FDA) for
the use of Lucentis in the treatment of neovascular wet AMD. The BLA
submission, which included a request for Priority (six-month) Review, is based
on one-year clinical data on the efficacy and safety of Lucentis from two
pivotal Phase III trials, ANCHOR and MARINA, as well as one-year clinical data
from the Phase I/II FOCUS trial.
About the Study
ANCHOR (ANti-VEGF Antibody for the Treatment of Predominantly Classic
CHORoidal Neovascularization in AMD) is a Phase III randomized, two-year,
multi-center, double-masked, active-treatment controlled study comparing two
different doses of Lucentis to PDT in 423 patients with predominantly classic
wet AMD. Patients were randomized 2:1 to receive intravitreal Lucentis
injections (0.3 mg or 0.5 mg dose) once a month or PDT every three months for
two years. Exclusion criteria included prior subfoveal laser treatment, PDT or
experimental treatments for wet AMD. Visual acuity was measured using the
Early Treatment Diabetic Retinopathy Study (ETDRS) chart, the standard method
of quantifying visual acuity. The study is ongoing in the United States,
Europe and Australia. Based on the one-year results, patients in the PDT alone
arm of the study will have access to Lucentis for the remainder of the study.
Additional Phase III Studies
SAILOR
In November 2005, Genentech began enrollment in a Phase IIIb study,
SAILOR, to make Lucentis available to eligible patients. SAILOR (Safety
Assessment of Intravitreal Lucentis fOR AMD) is a Phase IIIb clinical study of
Lucentis for patients with all subtypes of new or recurrent active subfoveal
wet AMD. It is a one-year study designed to evaluate the safety of two
different doses (0.3 mg and 0.5 mg) of Lucentis administered once a month for
three months and thereafter as needed based on re-treatment criteria. The
study will be conducted at more than 100 sites in the United States and will
enroll up to 5,000 patients. Those interested in additional information about
the study can call toll-free 1-888-662-6728.
MARINA
In July 2005, Genentech announced positive preliminary one-year results
from the pivotal Phase III MARINA study (Minimally classic/occult trial of the
Anti-VEGF antibody Ranibizumab In the treatment of Neovascular AMD), a
randomized, two-year, multi-center, double-masked, sham-injection controlled
study evaluating the safety and efficacy of two different doses of Lucentis in
716 patients with minimally classic or occult wet AMD. Nearly 95 percent of
patients treated with Lucentis maintained or improved vision at 12 months.
Additional one-year results include:
— Twenty-five percent (59/238) of patients treated with 0.3 mg of
Lucentis and 34 percent (81/240) treated with 0.5 mg of Lucentis
improved vision by a gain of 15 letters or more compared to
approximately 5 percent (11/238) of patients in the control group as
measured by the ETDRS eye chart.
— Nearly 40 percent (188/478) of Lucentis-treated patients achieved a
visual acuity score of 20/40 or better compared to 11 percent (26/238)
in the control group.
— Patients treated with Lucentis gained an average of seven letters in
visual acuity compared to study entry, while those in the control
group lost an average of 10.5 letters.
— The majority of patients treated with Lucentis (74.8 percent in the
0.3 mg group and 71.3 percent in the 0.5 mg group) experienced a
letter improvement of zero or more compared to 28.6 percent in the
sham group.
In October 2005, Genentech announced that patients in the sham arm of the
MARINA study would be crossed over to active treatment with Lucentis.
Additional one-year data from the MARINA study will be presented at the Macula
Society Meeting in February.
PIER
Genentech is also conducting PIER (A Phase IIIb, Multi-center, Randomized,
Double-Masked, Sham Injection-Controlled Study of the Efficacy and Safety of
Ranibizumab in Subjects with Subfoveal Choroidal Neovascularization with or
without Classic CNV Secondary to Age-Related Macular Degeneration) with 184
patients in the United States. In this trial, Lucentis is administered once
per month for the first three months followed thereafter by doses once every
three months for a total of 24 months. Enrollment in this study is complete,
and preliminary results are expected in the second quarter of 2006.
Lucentis Safety Profile
In clinical trials to date, the most common side effects that occurred
more frequently in the Lucentis arms (0.3 mg and 0.5 mg) than in the control
arms were mild to moderate and included: conjunctival hemorrhage, eye pain,
increased intraocular pressure and vitreous floaters.
Serious ocular adverse events that occurred more frequently in the
Lucentis-treated arms were uncommon and included endophthalmitis and
intraocular inflammation (less than 1 percent for each). Among non-ocular
serious adverse events, cerebral vascular events and myocardial infarctions
were observed in all three arms of both the Phase III MARINA and ANCHOR
studies. The combined rate of these events in these two studies with monthly
dosing was similar in the control and the 0.3 mg Lucentis arms (1.3 percent
and 1.6 percent respectively) and slightly higher in the 0.5 mg Lucentis arm
(2.9 percent).
About AMD
AMD is a major cause of painless central visual loss and is the leading
cause of blindness for people over the age of 60. The National Eye Institute
estimates that there are 1.6 million people with AMD in the United States
alone and that this prevalence will grow to 2.95 million by 2020. AMD occurs
in two forms: dry and wet.
The dry form is associated with atrophic cell death of the central retina
or macula, which is required for fine vision used for activities such as
reading, driving or recognizing faces. The wet form is caused by growth of
abnormal blood vessels, also known as choroidal neovascularization (CNV) or
ocular angiogenesis, under the macula. These vessels leak fluid and blood and
cause scar tissue that destroys the central retina. This results in a
deterioration of sight over a period of months to years.
About Lucentis
Lucentis(TM) (ranibizumab) is a humanized therapeutic antibody fragment
developed at Genentech and designed to bind and inhibit VEGF-A, a protein that
is believed to play a critical role in angiogenesis (the formation of new
blood vessels). Lucentis is designed to block new blood vessel growth and
leakiness, which lead to wet AMD disease progression and vision loss. Lucentis
is being developed by Genentech and the Novartis Ophthalmics Business Unit for
diseases or disorders of the eye. Genentech retains commercial rights in the
United States and Canada, and Novartis has exclusive commercial rights for the
rest of the world.
About Angiogenesis
Genentech is a leader in research and product development in the area of
angiogenesis, the process by which new blood vessels are formed. In 1989
Napoleone Ferrara, M.D., and a team of scientists at Genentech conducted
seminal work in the field, which resulted in the identification and cloning of
a gene termed Vascular Endothelial Growth Factor (VEGF), now known as VEGF-A.
The VEGF-A protein is believed to play a critical role in angiogenesis and
serves as one of the key contributors to physiological or pathological
conditions that can stimulate the formation of new blood vessels. The process
of angiogenesis is normally regulated throughout development and adult life,
and the uncontrolled growth of new blood vessels is an important contributor
to a number of pathologic conditions, including wet AMD.
About Genentech
Genentech is a leading biotechnology company that discovers, develops,
manufactures and commercializes biotherapeutics for significant unmet medical
needs. A considerable number of the currently approved biotechnology products
originated from or are based on Genentech science. Genentech manufactures and
commercializes multiple biotechnology products and licenses several additional
products to other companies. The company has headquarters in South San
Francisco, California and is listed on the New York Stock Exchange under the
symbol DNA. For additional information about the company, please visit
gene.
This press release contains forward-looking statements regarding Lucentis
as a potential therapy and the expected time frame for the PIER trial results.
Such statements are just predictions and involve risks and uncertainties such
that actual results may differ materially. Among other things, the time frame
for the PIER results could be affected by unexpected safety or efficacy
issues, additional time requirements to achieve study endpoints or for data
analysis, or discussions with the FDA or FDA actions; and Lucentis as a
potential therapy could be affected by all of the forgoing and the failure to
receive FDA approval, competition, pricing and the ability to supply product
or a product withdrawal. Please also refer to Genentech’s periodic reports
filed with the Securities and Exchange Commission. Genentech disclaims, and
does not undertake, any obligation to update or revise the forward-looking
statements in this press release.
Genentech, Inc.
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