New Preliminary Phase III MARINA Data Show the Improvement in Visual Acuity
Endpoints in Lucentis Groups Was Maintained at Year Two While Patients
in the Control Group Continued to Decline
SOUTH SAN FRANCISCO, Calif., Feb. 28 /PRNewswire-FirstCall/ -- Genentech,
Inc. (NYSE: DNA) announced today that the U.S. Food and Drug Administration
(FDA) has accepted the Biologics License Application (BLA) for the use of
Lucentis(TM) (ranibizumab) in the treatment of neovascular wet age-related
macular degeneration (AMD). As part of the BLA filing, Genentech requested
and has been granted a six-month Priority Review.
The FDA grants Priority Review to products that are considered to be
potentially significant therapeutic advancements over existing approved
therapies in the treatment, diagnosis or prevention of a disease. The FDA has
six months from the submission date, or by the end of June 2006, to take
action on the filing. The BLA was received by the FDA on December 30, 2005.
In addition, Genentech announced today that preliminary two-year data from
the Phase III MARINA study showed that the improvement in the Lucentis groups
at year one was maintained at year two as measured by visual acuity endpoints,
while there was further deterioration of vision among patients in the control
group. The difference between mean visual acuity in the Lucentis arms and the
control arm increased at year two compared to year one. At least 90 percent of
patients treated with Lucentis maintained (defined as a loss of less than 15
letters in visual acuity) or improved (defined as a gain of more than 15
letters in visual acuity) vision compared to approximately 53 percent of those
treated in the control arm at year two [p<0.0001].
"The FDA's decision to grant Priority Review underscores the potential
significant advancement of Lucentis in the treatment of wet AMD and puts us
one step closer to making available a therapy that may change outcomes for
people with this devastating disease," said Hal Barron, M.D., Genentech's
senior vice president of Development and chief medical officer. "The new
two-year Phase III MARINA results provide us with additional important data
from an ongoing rigorous clinical trial program that has consistently shown
Lucentis improved or maintained vision for the majority of patients who
otherwise may have faced blindness."
Consistent with year-one safety findings, common side effects that
occurred more frequently in the Lucentis groups than in the control group at
year two were mild to moderate and included conjunctival hemorrhage, increased
intraocular pressure and vitreous floaters. Serious ocular adverse events in
the MARINA study that occurred more frequently in the Lucentis-treated arms
were uncommon and included endophthalmitis (cumulative 1.3 percent or less
over two years) and intraocular inflammation (cumulative 1.7 percent or less
over two years). Among non-ocular serious adverse events, the combined
cumulative rate of cerebral vascular events and myocardial infarctions at two
years was 3 percent (7/236) in the sham injection group, 4.6 percent (11/238)
in the 0.3 mg Lucentis group and 4.2 percent (10/239) in the 0.5 mg group.
Genentech will submit two-year data from the Phase III MARINA study to the
FDA. These data will be presented during the Annual Meeting of the Association
for Research in Vision and Ophthalmology (ARVO) to be held in May 2006 in Fort
Lauderdale, Fla.
The Genentech BLA submission for Lucentis was based on one-year clinical
efficacy and safety data from two pivotal Phase III trials, ANCHOR and MARINA,
as well as one-year clinical data from the Phase I/II FOCUS trial. Data from
these studies demonstrate that Lucentis is the first investigational therapy
to have improved vision in patients with wet AMD in two pivotal Phase III
clinical trials. In addition, Lucentis is the first investigational therapy
to have demonstrated a clinical benefit compared to verteporfin (Visudyne(R))
photodynamic therapy (PDT) in a head-to-head clinical study (ANCHOR).
MARINA
MARINA (Minimally classic/occult trial of the Anti-VEGF antibody
Ranibizumab In the treatment of Neovascular AMD) is a Phase III study of 716
patients in the United States with minimally classic or occult wet AMD who
were randomized 2:1 to receive intravitreal Lucentis injections or a control
regimen. The control regimen consisted of a sham injection, meaning the
treating physician prepares and anesthetizes the patient's eye but does not
perform an injection. Patients treated with Lucentis were further randomized
to receive either a 0.3 mg or 0.5 mg dose of Lucentis once a month for two
years. In October 2005, Genentech announced that patients in the sham arm of
the MARINA study would be crossed over to active treatment with Lucentis.
In July 2005, Genentech presented positive preliminary one-year results
from MARINA in which 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.
ANCHOR
Earlier this year, Genentech announced positive preliminary one-year Phase
III data on Lucentis from ANCHOR, a study comparing two different doses of
Lucentis to verteporfin (Visudyne(R)) photodynamic therapy (PDT) in 423
patients with predominantly classic wet AMD. Approximately 94 percent of
patients treated with 0.3 mg of Lucentis and 96 percent of those treated with
0.5 mg of Lucentis maintained or improved vision (defined as a loss of less
than 15 letters in visual acuity) compared to approximately 64 percent of
those treated with PDT. Data from the ANCHOR study also 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.
An analysis of 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).
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 were offered
Lucentis for the remainder of the study.
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. The one-year study is 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.
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 1.7 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.
First Year Lucentis Safety Profile from Phase III Clinical Program
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 at one year). 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 at one year. 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 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, Calif., and is listed on the New York Stock Exchange under the
symbol DNA. For additional information about the company, please visit
http://www.gene.com .
This press release contains forward-looking statements within the meaning
of the Private Securities Litigation Reform Act of 1995 regarding Lucentis as
a potential therapy. Actual results may differ materially. Among other
things, Lucentis as a potential therapy could be affected by unexpected
safety, efficacy or manufacturing issues, discussions with the FDA, FDA
actions or delays, the failure to receive FDA approval, competition, pricing,
reimbursement or the ability to supply product. 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.
Media Contact: Dawn Kalmar 650-225-5873
Investor Contact: Kathee Littrell 650-225-1034
Patient Inquiries: 1-888-662-6728
SOURCE Genentech, Inc.
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Related links:
http://www.gene.com
CONTACT:
media, Dawn Kalmar, +1-650-225-5873, or
investors, Kathee Littrell, +1-650-225-1034, both of Genentech
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